Pathway modulations and epigenetic alterations in ovarian tumorbiogenesis

Journal of Cellular Physiology

Volumn 229, Issue 4, 2014, Pages 393-406

  Saldanha, Sabita N ^a,b   Tollefsbol, Trygve O ^a,c  

^a UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^b ALABAMA STATE UNIVERSITY   (United States)

^c UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ABC TRANSPORTER; BRCA1 PROTEIN; CYCLIN D1; G PROTEIN COUPLED RECEPTOR; GLYCOGEN SYNTHASE KINASE 3BETA; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN 6; MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; MICRORNA; MITOGEN ACTIVATED PROTEIN KINASE; MULTIDRUG RESISTANCE PROTEIN; NOTCH RECEPTOR; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN BAX; PROTEIN BCL 2; PROTEIN KINASE B; PROTEIN P21; PROTEIN P27; PROTEIN P53; SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR FOXM1; TUMOR SUPPRESSOR PROTEIN; UNCLASSIFIED DRUG;

CANCER DIAGNOSIS; CANCER PROGNOSIS; CANCER STEM CELL; CANCER SURVIVAL; CARCINOGENESIS; CELL CYCLE; CELL DIVISION; CELL GROWTH; CELL POPULATION; CELL PROLIFERATION; COMPLEX FORMATION; DNA BINDING; DNA METHYLATION; EPIGENETICS; EXCISION REPAIR; GENE MUTATION; HISTONE MODIFICATION; HUMAN; MESOTHELIUM; MISSENSE MUTATION; NONHUMAN; OVARY ADENOCARCINOMA; OVARY CANCER; OVARY CARCINOMA; PHENOTYPE; POINT MUTATION; PREMATURE OVARIAN FAILURE; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN PHOSPHORYLATION; PROTO ONCOGENE; REVIEW; SURVIVAL RATE; TREATMENT RESPONSE; TUMOR SUPPRESSOR GENE; WNT SIGNALING PATHWAY;

EID: 84890513431     PISSN: 00219541     EISSN: 10974652     Source Type: Journal    
DOI: 10.1002/jcp.24466     Document Type: Review

References (223)

1. Abe A, Minaguchi T, Ochi H, Onuki M, Okada S, Matsumoto K, Satoh T, Oki A, Yoshikawa H. 2013. PIK3CA overexpression is a possible prognostic factor for favorable survival in ovarian clear cell carcinoma. Hum Pathol 44:199-207.
2. Abramovitch S, Werner H. 2003. Functional and physical interactions between BRCA1 and p53 in transcriptional regulation of the IGF-IR gene. Horm Metab Res 35:758-762.
3. Amikura T, Sekine M, Hirai Y, Fujimoto S, Hatae M, Kobayashi I, Fujii T, Nagata I, Ushijima K, Obata K, Suzuki M, Yoshinaga M, Umesaki N, Satoh S, Enomoto T, Motoyama S, Nishino K, Haino K, Tanaka K, G. Japanese Familial Ovarian Cancer Study. 2006. Mutational analysis of TP53 and p21 in familial and sporadic ovarian cancer in Japan. Gynecol Oncol 100:365-371.
4. Anttila MA, Ji H, Juhola MT, Saarikoski SV, Syrjanen KJ. 1999a. The prognostic significance of p53 expression quantitated by computerized image analysis in epithelial ovarian cancer. Int J Gynecol Pathol 18:42-51.
5. Anttila MA, Kosma VM, Hongxiu J, Puolakka J, Juhola M, Saarikoski S, Syrjanen K. 1999b. p21/WAF1 expression as related to p53, cell proliferation and prognosis in epithelial ovarian cancer. Br J Cancer 79:1870-1878.
6. Auner V, Kriegshauser G, Tong D, Horvat R, Reinthaller A, Mustea A, Zeillinger R. 2009. KRAS mutation analysis in ovarian samples using a high sensitivity biochip assay. BMC Cancer 9:111-118.
7. Auner V, Sehouli J, Oskay-Oezcelik G, Horvat R, Speiser P, Zeillinger R. 2010. ABC transporter gene expression in benign and malignant ovarian tissue. Gynecol Oncol 117:198-201.
8. Baekelandt M, Holm R, Trope CG, Nesland JM, Kristensen GB. 1999. Lack of independent prognostic significance of p21 and p27 expression in advanced ovarian cancer: An immunohistochemical study. Clin Cancer Res 5:2848-2853.
9. Baer C, Claus R, Plass C. 2013. Genome-wide epigenetic regulation of miRNAs in cancer. Cancer Res 73:473-477.
10. Balch C, Nephew KP. 2010. The role of chromatin, microRNAs, and tumor stem cells in ovarian cancer. Cancer Biomark 8:203-221.
11. Bali A, O'Brien PM, Edwards LS, Sutherland RL, Hacker NF, Henshall SM. 2004. Cyclin D1, p53, and p21Waf1/Cip1 expression is predictive of poor clinical outcome in serous epithelial ovarian cancer. Clin Cancer Res 10:5168-5177.
12. Bammidi LS, Neerukonda GN, Murthy S, Kanapuram RD. 2012. p16 gene alterations in human ovarian cancers: Comparison between tissue and blood samples. Int J Gynecol Cancer 22:553-560.
13. Barbieri F, Lorenzi P, Ragni N, Schettini G, Bruzzo C, Pedulla F, Alama A. 2004. Overexpression of cyclin D1 is associated with poor survival in epithelial ovarian cancer. Oncology 66:310-315.
14. Bartkova J, Rajpert-De Meyts E, Skakkebaek NE, Lukas J, Bartek J. 2003. Deregulation of the G1/S-phase control in human testicular germ cell tumours. APMIS 111:252-265; discussion 265-256.
15. Basu A, Krishnamurthy S. 2010. Cellular responses to cisplatin-induced DNA damage. J Nucleic Acids 2010:1-16.
16. Berenjeno IM, Vanhaesebroeck B. 2009. PI3K regulatory subunits lose control in cancer. Cancer Cell 16:449-450.
17. Blanco-Aparicio C, Renner O, Leal JF, Carnero A. 2007. PTEN, more than the AKT pathway. Carcinogenesis 28:1379-1386.
18. Borman SM, Christian PJ, Sipes IG, Hoyer PB. 2000. Ovotoxicity in female Fischer rats and B6 mice induced by low-dose exposure to three polycyclic aromatic hydrocarbons: Comparison through calculation of an ovotoxic index. Toxicol Appl Pharmacol 167:191-198.
19. Brugarolas J, Jacks T. 1997. Double indemnity: p53, BRCA and cancer. p53 mutation partially rescues developmental arrest in Brca1 and Brca2 null mice, suggesting a role for familial breast cancer genes in DNA damage repair. Nat Med 3:721-722.
20. Carden CP, Stewart A, Thavasu P, Kipps E, Pope L, Crespo M, Miranda S, Attard G, Garrett MD, Clarke PA, Workman P, de Bono JS, Gore M, Kaye SB, Banerji U. 2012. The association of PI3 kinase signaling and chemoresistance in advanced ovarian cancer. Mol Cancer Ther 11:1609-1617.
21. Cariou S, Donovan JC, Flanagan WM, Milic A, Bhattacharya N, Slingerland JM. 2000. Down-regulation of p21WAF1/CIP1 or p27Kip1 abrogates antiestrogen-mediated cell cycle arrest in human breast cancer cells. Proc Natl Acad Sci USA 97:9042-9046.
22. Carnero A. 2010. The PKB/AKT pathway in cancer. Curr Pharm Des 16:34-44.
23. Caslini C, Capo-chichi CD, Roland IH, Nicolas E, Yeung AT, Xu XX. 2006. Histone modifications silence the GATA transcription factor genes in ovarian cancer. Oncogene 25:5446-5461.
24. Chapman-Rothe N, Curry E, Zeller C, Liber D, Stronach E, Gabra H, Ghaem-Maghami S, Brown R. 2012. Chromatin H3K27me3/H3K4me3 histone marks define gene sets in high-grade serous ovarian cancer that distinguish malignant, tumour-sustaining and chemo-resistant ovarian tumour cells. Oncogene 32:4586-4592.
25. Chen X, Horiuchi A, Kikuchi N, Osada R, Yoshida J, Shiozawa T, Konishi I. 2007. Hedgehog signal pathway is activated in ovarian carcinomas, correlating with cell proliferation: It's inhibition leads to growth suppression and apoptosis. Cancer Sci 98:68-76.
26. Chen R, Alvero AB, Silasi DA, Kelly MG, Fest S, Visintin I, Leiser A, Schwartz PE, Rutherford T, Mor G. 2008. Regulation of IKKbeta by miR-199a affects NF-kappaB activity in ovarian cancer cells. Oncogene 27:4712-4723.
27. Chen H, Hardy TM, Tollefsbol TO. 2011. Epigenomics of ovarian cancer and its chemoprevention. Front Genet 2:1-8.
28. Chen Q, Gao G, Luo S. 2013a. Hedgehog signaling pathway and ovarian cancer. Chin J Cancer Res 25:346-353.
29. Chen Y, Bieber MM, Teng NN. 2013b. Hedgehog signaling regulates drug sensitivity by targeting ABC transporters ABCB1 and ABCG2 in epithelial ovarian cancer. Mol Carcinog 1-8.
30. Cheng SY, Yue S. 2008. Role and regulation of human tumor suppressor SUFU in Hedgehog signaling. Adv Cancer Res 101:29-43.
31. Cherblanc F, Chapman-Rothe N, Brown R, Fuchter MJ. 2012. Current limitations and future opportunities for epigenetic therapies. Future Med Chem 4:425-446.
32. Chmelarova M, Krepinska E, Spacek J, Laco J, Nekvindova J, Palicka V. 2012. Methylation analysis of tumour suppressor genes in ovarian cancer using MS-MLPA. Folia Biol (Praha) 58:246-250.
33. Christiansen AE, Ding T, Bergmann A. 2012. Ligand-independent activation of the Hedgehog pathway displays non-cell autonomous proliferation during eye development in Drosophila. Mech Dev 129:98-108.
34. Coni S, Infante P, Gulino A. 2013. Control of stem cells and cancer stem cells by Hedgehog signaling: Pharmacologic clues from pathway dissection. Biochem Pharmacol 85:623-628.
35. Corney DC, Flesken-Nikitin A, Godwin AK, Wang W, Nikitin AY. 2007. MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res 67:8433-8438.
36. Cramer DW. 2012. The epidemiology of endometrial and ovarian cancer. Hematol Oncol Clin North Am 26:1-12.
37. Creighton CJ, Fountain MD, Yu Z, Nagaraja AK, Zhu H, Khan M, Olokpa E, Zariff A, Gunaratne PH, Matzuk MM, Anderson ML. 2010. Molecular profiling uncovers a p53-associated role for microRNA-31 in inhibiting the proliferation of serous ovarian carcinomas and other cancers. Cancer Res 70:1906-1915.
38. Dai W, Teodoridis JM, Zeller C, Graham J, Hersey J, Flanagan JM, Stronach E, Millan DW, Siddiqui N, Paul J, Brown R. 2011. Systematic CpG islands methylation profiling of genes in the wnt pathway in epithelial ovarian cancer identifies biomarkers of progression-free survival. Clin Cancer Res 17:4052-4062.
39. Davies AA, Masson JY, McIlwraith MJ, Stasiak AZ, Stasiak A, Venkitaraman AR, West SC. 2001. Role of BRCA2 in control of the RAD51 recombination and DNA repair protein. Mol Cell 7:273-282.
40. De La Rosa-Velazquez IA, Rincon-Arano H, Benitez-Bribiesca L, Recillas-Targa F. 2007. Epigenetic regulation of the human retinoblastoma tumor suppressor gene promoter by CTCF. Cancer Res 67:2577-2585.
41. Dent P, Grant S, Fisher PB, Curiel DT. 2009. PI3K: A rational target for ovarian cancer therapy? Cancer Biol Ther 8:27-30.
42. Djordjevic B, Stojanovic S, Conic I, Jankovic-Velickovic L, Vukomanovic P, Zivadinovic R, Vukadinovic M. 2012. Current approach to epithelial ovarian cancer based on the concept of cancer stem cells. J BUON 17:627-636.
43. Dobbin ZC, Landen CN. 2013. The importance of the PI3K/AKT/MTOR pathway in the progression of ovarian cancer. Int J Mol Sci 14:8213-8227.
44. Edkins S, O'Meara S, Parker A, Stevens C, Reis M, Jones S, Greenman C, Davies H, Dalgliesh G, Forbes S, Hunter C, Smith R, Stephens P, Goldstraw P, Nicholson A, Chan TL, Velculescu VE, Yuen ST, Leung SY, Stratton MR, Futreal PA. 2006. Recurrent KRAS codon 146 mutations in human colorectal cancer. Cancer Biol Ther 5:928-932.
45. Ehtesham M, Sarangi A, Valadez JG, Chanthaphaychith S, Becher MW, Abel TW, Thompson RC, Cooper MK. 2007. Ligand-dependent activation of the hedgehog pathway in glioma progenitor cells. Oncogene 26:5752-5761.
46. Eltabbakh GH, Belinson JL, Kennedy AW, Biscotti CV, Casey G, Tubbs RR, Blumenson LE. 1997. p53 overexpression is not an independent prognostic factor for patients with primary ovarian epithelial cancer. Cancer 80:892-898.
47. Enoiu M, Jiricny J, Scharer OD. 2012. Repair of cisplatin-induced DNA interstrand crosslinks by a replication-independent pathway involving transcription-coupled repair and translesion synthesis. Nucleic Acids Res 40:8953-8964.
48. Fleischer AC, Lyshchik A, Hirari M, Moore RD, Abramson RG, Fishman DA. 2012. Early detection of ovarian cancer with conventional and contrast-enhanced transvaginal sonography: Recent advances and potential improvements. J Oncol 2012:1-11.
49. Fleming RJ, Purcell K, Artavanis-Tsakonas S. 1997. The NOTCH receptor and its ligands. Trends Cell Biol 7:437-441.
50. Folgiero V, Di Carlo SE, Bon G, Spugnini EP, Di Benedetto A, Germoni S, Pia Gentileschi M, Accardo A, Milella M, Morelli G, Bossi G, Mottolese M, Falcioni R. 2012. Inhibition of p85, the non-catalytic subunit of phosphatidylinositol 3-kinase, exerts potent antitumor activity in human breast cancer cells. Cell Death Dis 3:1-9.
51. Foster R, Buckanovich RJ, Rueda BR. 2012. Ovarian cancer stem cells: Working towards the root of stemness. Cancer Lett 338:147-157.
52. Fu X, Tian J, Zhang L, Chen Y, Hao Q. 2012. Involvement of microRNA-93, a new regulator of PTEN/Akt signaling pathway, in regulation of chemotherapeutic drug cisplatin chemosensitivity in ovarian cancer cells. FEBS Lett 586:1279-1286.
53. Gallagher MF, Heffron CC, Laios A, O'Toole SA, Ffrench B, Smyth PC, Flavin RJ, Elbaruni SA, Spillane CD, Martin CM, Sheils OM, O'Leary JJ. 2012. Suppression of cancer stemness p21-regulating mRNA and microRNA signatures in recurrent ovarian cancer patient samples. J Ovarian Res 5:1-11.
54. Gray GE, Mann RS, Mitsiadis E, Henrique D, Carcangiu ML, Banks A, Leiman J, Ward D, Ish-Horowitz D, Artavanis-Tsakonas S. 1999. Human ligands of the Notch receptor. Am J Pathol 154:785-794.
55. Harris TJ, McCormick F. 2010. The molecular pathology of cancer. Nat Rev Clin Oncol 7:251-265.
56. Hartmann LC, Podratz KC, Keeney GL, Kamel NA, Edmonson JH, Grill JP, Su JQ, Katzmann JA, Roche PC. 1994. Prognostic significance of p53 immunostaining in epithelial ovarian cancer. J Clin Oncol 12:64-69.
57. Hashiguchi Y, Tsuda H, Yamamoto K, Inoue T, Ishiko O, Ogita S. 2001. Combined analysis of p53 and RB pathways in epithelial ovarian cancer. Hum Pathol 32:988-996.
58. Hashimoto T, Yanaihara N, Okamoto A, Nikaido T, Saito M, Takakura S, Yasuda M, Sasaki H, Ochiai K, Tanaka T. 2011. Cyclin D1 predicts the prognosis of advanced serous ovarian cancer. Exp Ther Med 2:213-219.
59. Havrilesky L, Darcy k M, Hamdan H, Priore RL, Leon J, Bell J, Berchuck A, S. Gynecologic Oncology Group. 2003. Prognostic significance of p53 mutation and p53 overexpression in advanced epithelial ovarian cancer: A Gynecologic Oncology Group Study. J Clin Oncol 21:3814-3825.
60. He J, de la Monte S, Wands JR. 2010. The p85beta regulatory subunit of PI3K serves as a substrate for PTEN protein phosphatase activity during insulin mediated signaling. Biochem Biophys Res Commun 397:513-519.
61. Hilliard TS, Modi DA, Burdette JE. 2013. Gonadotropins activate oncogenic pathways to enhance proliferation in normal mouse ovarian surface epithelium. Int J Mol Sci 14:4762-4782.
62. Hindley C, Philpott A. 2012. Co-ordination of cell cycle and differentiation in the developing nervous system. Biochem J 444:375-382.
63. Hinz JM. 2010. Role of homologous recombination in DNA interstrand crosslink repair. Environ Mol Mutagen 51:582-603.
64. Hofmann BT, Jucker M. 2012. Activation of PI3K/Akt signaling by n-terminal SH2 domain mutants of the p85alpha regulatory subunit of PI3K is enhanced by deletion of its c-terminal SH2 domain. Cell Signal 24:1950-1954.
65. Hopfer O, Zwahlen D, Fey MF, Aebi S. 2005. The Notch pathway in ovarian carcinomas and adenomas. Br J Cancer 93:709-718.
66. Houshdaran S, Hawley S, Palmer C, Campan M, Olsen MN, Ventura AP, Knudsen BS, Drescher CW, Urban ND, Brown PO, Laird PW. 2010. DNA methylation profiles of ovarian epithelial carcinoma tumors and cell lines. PLoS ONE 5:1-16.
67. Huang J, Zhang L, Greshock J, Colligon TA, Wang Y, Ward R, Katsaros D, Lassus H, Butzow R, Godwin AK, Testa JR, Nathanson KL, Gimotty PA, Coukos G, Weber BL, Degenhardt Y. 2011. Frequent genetic abnormalities of the PI3K/AKT pathway in primary ovarian cancer predict patient outcome. Genes Chromosomes Cancer 50:606-618.
68. Huang RL, Gu F, Kirma NB, Ruan J, Chen CL, Wang HC, Liao YP, Chang CC, Yu MH, Pilrose JM, Thompson IM, Huang HC, Huang TH, Lai HC, Nephew KP. 2013. Comprehensive methylome analysis of ovarian tumors reveals hedgehog signaling pathway regulators as prognostic DNA methylation biomarkers. Epigenetics 8:624-634.
69. Hussain AR, Ahmed SO, Ahmed M, Khan OS, Al Abdulmohsen S, Platanias LC, Al-Kuraya KS, Uddin S. 2012. Cross-talk between NFkB and the PI3-kinase/AKT pathway can be targeted in primary effusion lymphoma (PEL) cell lines for efficient apoptosis. PLoS ONE 7:1-12.
70. Ito A, Kawaguchi Y, Lai CH, Kovacs JJ, Higashimoto Y, Appella E, Yao TP. 2002. MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation. EMBO J 21:6236-6245.
71. Janku F, Tsimberidou AM, Garrido-Laguna I, Wang X, Luthra R, Hong DS, Naing A, Falchook GS, Moroney JW, Piha-Paul SA, Wheler JJ, Moulder SL, Fu S, Kurzrock R. 2011. PIK3CA mutations in patients with advanced cancers treated with PI3K/AKT/mTOR axis inhibitors. Mol Cancer Ther 10:558-565.
72. Janku F, Wheler JJ, Westin SN, Moulder SL, Naing A, Tsimberidou AM, Fu S, Falchook GS, Hong DS, Garrido-Laguna I, Luthra R, Lee JJ, Lu KH, Kurzrock R. 2012. PI3K/AKT/mTOR inhibitors in patients with breast and gynecologic malignancies harboring PIK3CA mutations. J Clin Oncol 30:777-782.
73. Januchowski R, Wojtowicz K, Sujka-Kordowska P, Andrzejewska M, Zabel M. 2013. MDR gene expression analysis of six drug-resistant ovarian cancer cell lines. Biomed Res Int 2013:241763.
74. Jasin M. 2002. Homologous repair of DNA damage and tumorigenesis: The BRCA connection. Oncogene 21:8981-8993.
75. Jayasurya R, Francis G, Kannan S, Lekshminarayanan K, Nalinakumari KR, Abraham T, Abraham EK, Nair MK. 2004. p53, p16 and cyclin D1: Molecular determinants of radiotherapy treatment response in oral carcinoma. Int J Cancer 109:710-716.
76. Johannsson OT, Idvall I, Anderson C, Borg A, Barkardottir RB, Egilsson V, Olsson H. 1997. Tumour biological features of BRCA1-induced breast and ovarian cancer. Eur J Cancer 33:362-371.
77. Johnson N, Li YC, Walton ZE, Cheng KA, Li D, Rodig SJ, Moreau LA, Unitt C, Bronson RT, Thomas HD, Newell DR, D'Andrea AD, Curtin NJ, Wong KK, Shapiro GI. 2011. Compromised CDK1 activity sensitizes BRCA-proficient cancers to PARP inhibition. Nat Med 17:875-882.
78. Jones S, Wang TL, Kurman RJ, Nakayama K, Velculescu VE, Vogelstein B, Kinzler KW, Papadopoulos N, Shih Ie M. 2012. Low-grade serous carcinomas of the ovary contain very few point mutations. J Pathol 226:413-420.
79. Kaern J, Aghmesheh M, Nesland JM, Danielsen HE, Sandstad B, Friedlander M, Trope C. 2005. Prognostic factors in ovarian carcinoma stage III patients. Can biomarkers improve the prediction of short- and long-term survivors? Int J Gynecol Cancer 15:1014-1022.
80. Kawauchi S, Liu XP, Kawasaki K, Hirakawa T, Amada S, Furuya T, Oga A, Sasaki K. 2004. Significance of beta-catenin and pRB pathway components in malignant ovarian germ cell tumours: INK4A promoter CpG island methylation is associated with cell proliferation. J Pathol 204:268-276.
81. Kayani M, Kayani MA, Malik FA, Faryal R. 2011. Role of miRNAs in breast cancer. Asian Pac J Cancer Prev 12:3175-3180.
82. Keane FK, Ratner ES. 2010. The KRAS-variant genetic test as a marker of increased risk of ovarian cancer. Rev Obstet Gynecol 3:118-121.
83. Kim JH, Yoon EK, Chung HJ, Park SY, Hong KM, Lee CH, Lee YS, Choi K, Yang Y, Kim K, Kim IH. 2013. p53 acetylation enhances Taxol-induced apoptosis in human cancer cells. Apoptosis 18:110-120.
84. Kinross KM, Brown DV, Kleinschmidt M, Jackson S, Christensen J, Cullinane C, Hicks RJ, Johnstone RW, McArthur GA. 2011. In vivo activity of combined PI3K/mTOR and MEK inhibition in a Kras(G12D);Pten deletion mouse model of ovarian cancer. Mol Cancer Ther 10:1440-1449.
85. Kohler MF, Kerns BJ, Humphrey PA, Marks JR, Bast RC, Jr., Berchuck A. 1993. Mutation and overexpression of p53 in early-stage epithelial ovarian cancer. Obstet Gynecol 81:643-650.
86. Konecny GE, Winterhoff B, Kolarova T, Qi J, Manivong K, Dering J, Yang G, Chalukya M, Wang HJ, Anderson L, Kalli KR, Finn RS, Ginther C, Jones S, Velculescu VE, Riehle D, Cliby WA, Randolph S, Koehler M, Hartmann LC, Slamon DJ. 2011. Expression of p16 and retinoblastoma determines response to CDK4/6 inhibition in ovarian cancer. Clin Cancer Res 17:1591-1602.
87. Kuhlmann JD, Rasch J, Wimberger P, Kasimir-Bauer S. 2012. microRNA and the pathogenesis of ovarian cancer-A new horizon for molecular diagnostics and treatment? Clin Chem Lab Med 50:601-615.
88. Kuhn E, Kurman RJ, Vang R, Sehdev AS, Han G, Soslow R, Wang TL, Shih Ie M. 2012. TP53 mutations in serous tubal intraepithelial carcinoma and concurrent pelvic high-grade serous carcinoma-Evidence supporting the clonal relationship of the two lesions. J Pathol 226:421-426.
89. Kundu ST, Nallur S, Paranjape T, Boeke M, Weidhaas JB, Slack FJ. 2012. KRAS alleles: The LCS6 3′UTR variant and KRAS coding sequence mutations in the NCI-60 panel. Cell Cycle 11:361-366.
90. Kurman RJ, Shih Ie M. 2010. The origin and pathogenesis of epithelial ovarian cancer: A proposed unifying theory. Am J Surg Pathol 34:433-443.
91. Kurman RJ, Shih Ie M. 2011. Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer-shifting the paradigm. Hum Pathol 42:918-931.
92. Kurose K, Zhou XP, Araki T, Cannistra SA, Maher ER, Eng C. 2001. Frequent loss of PTEN expression is linked to elevated phosphorylated Akt levels, but not associated with p27 and cyclin D1 expression, in primary epithelial ovarian carcinomas. Am J Pathol 158:2097-2106.
93. Kusume T, Tsuda H, Kawabata M, Inoue T, Umesaki N, Suzuki T, Yamamoto K. 1999. The p16-cyclin D1/CDK4-pRb pathway and clinical outcome in epithelial ovarian cancer. Clin Cancer Res 5:4152-4157.
94. Kwok JM, Peck B, Monteiro LJ, Schwenen HD, Millour J, Coombes RC, Myatt SS, Lam EW. 2010. FOXM1 confers acquired cisplatin resistance in breast cancer cells. Mol Cancer Res 8:24-34.
95. Laios A, Mohamed BM, Kelly L, Flavin R, Finn S, McEvoy L, Gallagher M, Martin C, Sheils O, Ring M, Davies A, Lawson M, Gleeson N, D'Arcy T, d'Adhemar C, Norris L, Langhe R, Saadeh FA, O'Leary JJ, O'Toole SA. 2013. Pre-treatment of platinum resistant ovarian cancer cells with an MMP-9/MMP-2 inhibitor prior to cisplatin enhances cytotoxicity as determined by high content screening. Int J Mol Sci 14:2085-2103.
96. Landen CN, Jr., Birrer MJ, Sood AK. 2008. Early events in the pathogenesis of epithelial ovarian carcinoma. J Clin Oncol 26:995-1005.
97. Laudanski P, Kowalczuk O, Klasa-Mazurkiewicz D, Milczek T, Rysak-Luberowicz D, Garbowicz M, Baranowski W, Charkiewicz R, Szamatowicz J, Chyczewski L. 2011. Selective gene expression profiling of mTOR-associated tumor suppressor and oncogenes in ovarian cancer. Folia Histochem Cytobiol 49:317-324.
98. Le Page C, Huntsman DG, Provencher DM, Mes-Masson AM. 2010. Predictive and prognostic protein biomarkers in epithelial ovarian cancer: Recommendation for future studies. Cancers 2:913-954.
99. le Sage C, Nagel R, Egan DA, Schrier M, Mesman E, Mangiola A, Anile C, Maira G, Mercatelli N, Ciafre SA, Farace MG, Agami R. 2007. Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO J 26:3699-3708.
100. Lee S, Choi EJ, Jin C, Kim DH. 2005. Activation of PI3K/Akt pathway by PTEN reduction and PIK3CA mRNA amplification contributes to cisplatin resistance in an ovarian cancer cell line. Gynecol Oncol 97:26-34.
101. Lee JY, Engelman JA, Cantley LC. 2007. Biochemistry. PI3K charges ahead. Science 317:206-207.
102. Leffers N, Lambeck AJ, de Graeff P, Bijlsma AY, Daemen T, van der Zee AG, Nijman HW. 2008. Survival of ovarian cancer patients overexpressing the tumour antigen p53 is diminished in case of MHC class I down-regulation. Gynecol Oncol 110:365-373.
103. Lendahl U. 1998. A growing family of Notch ligands. Bioessays 20:103-107.
104. Leong WF, Chau JF, Li B. 2009. p53 Deficiency leads to compensatory up-regulation of p16INK4a. Mol Cancer Res 7:354-360.
105. Li Q, Zhang N, Jia Z, Le X, Dai B, Wei D, Huang S, Tan D, Xie K. 2009. Critical role and regulation of transcription factor FoxM1 in human gastric cancer angiogenesis and progression. Cancer Res 69:3501-3509.
106. Li GH, Fan YZ, Liu XW, Zhang BF, Yin DD, He F, Huang SY, Kang ZJ, Xu H, Liu Q, Wu YL, Niu XL, Zhang L, Liu L, Hao MW, Han H, Liang YM. 2010. Notch signaling maintains proliferation and survival of the HL60 human promyelocytic leukemia cell line and promotes the phosphorylation of the Rb protein. Mol Cell Biochem 340:7-14.
107. Li HT, Lu YY, An YX, Wang X, Zhao QC. 2011. KRAS, BRAF and PIK3CA mutations in human colorectal cancer: Relationship with metastatic colorectal cancer. Oncol Rep 25:1691-1697.
108. Li J, Song J, Cassidy MG, Rychahou P, Starr ME, Liu J, Li X, Epperly G, Weiss HL, Townsend CM, Jr., Gao T, Evers BM. 2012. PI3K p110alpha/Akt signaling negatively regulates secretion of the intestinal peptide neurotensin through interference of granule transport. Mol Endocrinol 26:1380-1393.
109. Lilja T, Wallenborg K, Bjorkman K, Albage M, Eriksson M, Lagercrantz H, Rohdin M, Hermanson O. 2013. Novel alterations in the epigenetic signature of MeCP2-targeted promoters in lymphocytes of Rett syndrome patients. Epigenetics 8:246-251.
110. Liu Y, Ganesan TS. 2002. Tumour suppressor genes in sporadic epithelial ovarian cancer. Reproduction 123:341-353.
111. Liu FS, Kohler MF, Marks JR, Bast RC, Jr., Boyd J, Berchuck A. 1994. Mutation and overexpression of the p53 tumor suppressor gene frequently occurs in uterine and ovarian sarcomas. Obstet Gynecol 83:118-124.
112. Lok GT, Chan DW, Liu VW, Hui WW, Leung TH, Yao KM, Ngan HY. 2011. Aberrant activation of ERK/FOXM1 signaling cascade triggers the cell migration/invasion in ovarian cancer cells. PLoS ONE 6:1-10.
113. Lotem J, Sachs L. 2006. Epigenetics and the plasticity of differentiation in normal and cancer stem cells. Oncogene 25:7663-7672.
114. Mabuchi S, Hisamatsu T, Kimura T. 2011. Targeting mTOR signaling pathway in ovarian cancer. Curr Med Chem 18:2960-2968.
115. Mane SM, Meltzer SJ, Gutheil JC, Kapil V, Lee EJ, Needleman SW. 1990. RAS gene activation in acute myelogenous leukemia: Analysis by in vitro amplification and DNA base sequence determination. Genes Chromosomes Cancer 2:71-77.
116. Mangelberger D, Kern D, Loipetzberger A, Eberl M, Aberger F. 2012. Cooperative Hedgehog-EGFR signaling. Front Biosci (Landmark Ed) 17:90-99.
117. Maradeo ME, Cairns P. 2011. Translational application of epigenetic alterations: Ovarian cancer as a model. FEBS Lett 585:2112-2120.
118. Marks JR, Davidoff AM, Kerns BJ, Humphrey PA, Pence JC, Dodge RK, Clarke-Pearson DL, Iglehart JD, Bast RC, Jr., Berchuck A. 1991. Overexpression and mutation of p53 in epithelial ovarian cancer. Cancer Res 51:2979-2984.
119. Marsit CJ, Houseman EA, Christensen BC, Eddy K, Bueno R, Sugarbaker DJ, Nelson HH, Karagas MR, Kelsey KT. 2006. Examination of a CpG island methylator phenotype and implications of methylation profiles in solid tumors. Cancer Res 66:10621-10629.
120. McAuliffe SM, Morgan SL, Wyant GA, Tran LT, Muto KW, Chen YS, Chin KT, Partridge JC, Poole BB, Cheng KH, Daggett J, Jr., Cullen K, Kantoff E, Hasselbatt K, Berkowitz J, Muto MG, Berkowitz RS, Aster JC, Matulonis UA, Dinulescu DM. 2012. Targeting Notch, a key pathway for ovarian cancer stem cells, sensitizes tumors to platinum therapy. Proc Natl Acad Sci USA 109:E2939-E2948.
121. Mencalha AL, Binato R, Ferreira GM, Du Rocher B, Abdelhay E. 2012. Forkhead box M1 (FoxM1) gene is a new STAT3 transcriptional factor target and is essential for proliferation, survival and DNA repair of K562 cell line. PLoS ONE 7:1-10.
122. Meng Q, Xia C, Fang J, Rojanasakul Y, Jiang BH. 2006. Role of PI3K and AKT specific isoforms in ovarian cancer cell migration, invasion and proliferation through the p70S6K1 pathway. Cell Signal 18:2262-2271.
123. Milde-Langosch K, Hagen M, Bamberger AM, Loning T. 2003. Expression and prognostic value of the cell-cycle regulatory proteins, Rb, p16MTS1, p21WAF1, p27KIP1, cyclin E, and cyclin D2, in ovarian cancer. Int J Gynecol Pathol 22:168-174.
124. Millour J, de Olano N, Horimoto Y, Monteiro LJ, Langer JK, Aligue R, Hajji N, Lam EW. 2011. ATM and p53 regulate FOXM1 expression via E2F in breast cancer epirubicin treatment and resistance. Mol Cancer Ther 10:1046-1058.
125. Min KJ, So KA, Ouh YT, Hong JH, Lee JK. 2012. The effects of DNA methylation and epigenetic factors on the expression of CD133 in ovarian cancers. J Ovarian Res 5:1-8.
126. Mizumoto Y, Kyo S, Kiyono T, Takakura M, Nakamura M, Maida Y, Mori N, Bono Y, Sakurai H, Inoue M. 2011. Activation of NF-kappaB is a novel target of KRAS-induced endometrial carcinogenesis. Clin Cancer Res 17:1341-1350.
127. Modesitt SC, Ramirez P, Zu Z, Bodurka-Bevers D, Gershenson D, Wolf JK. 2001. In vitro and in vivo adenovirus-mediated p53 and p16 tumor suppressor therapy in ovarian cancer. Clin Cancer Res 7:1765-1772.
128. Modugno F, Edwards RP. 2012. Ovarian cancer: Prevention, detection, and treatment of the disease and its recurrence. Molecular mechanisms and personalized medicine meeting report. Int J Gynecol Cancer 22:S45-S57.
129. Navaraj A, Finnberg N, Dicker DT, Yang W, Matthew EM, El-Deiry WS. 2009. Reduced cell death, invasive and angiogenic features conferred by BRCA1-deficiency in mammary epithelial cells transformed with H-Ras. Cancer Biol Ther 8:2417-2444.
130. No JH, Jeon YT, Park IA, Kim YB, Kim JW, Park NH, Kang SB, Han JY, Lim JM, Song YS. 2011. Activation of mTOR signaling pathway associated with adverse prognostic factors of epithelial ovarian cancer. Gynecol Oncol 121:8-12.
131. Nowak-Markwitz E, Spaczynski M. 2012. Ovarian cancer-Modern approach to its origin and histogenesis. Ginekol Pol 83:454-457.
132. Oliveira-Cunha M, Hadfield KD, Siriwardena AK, Newman W. 2012. EGFR and KRAS mutational analysis and their correlation to survival in pancreatic and periampullary cancer. Pancreas 41:428-434.
133. Oudit GY, Sun H, Kerfant BG, Crackower MA, Penninger JM, Backx PH. 2004. The role of phosphoinositide-3 kinase and PTEN in cardiovascular physiology and disease. J Mol Cell Cardiol 37:449-471.
134. Ozdemir F, Altinisik J, Karateke A, Coksuer H, Buyru N. 2012. Methylation of tumor suppressor genes in ovarian cancer. Exp Ther Med 4:1092-1096.
135. Ozer H, Yenicesu G, Arici S, Cetin M, Tuncer E, Cetin A. 2012. Immunohistochemistry with apoptotic-antiapoptotic proteins (p53, p21, bax, bcl-2), c-kit, telomerase, and metallothionein as a diagnostic aid in benign, borderline, and malignant serous and mucinous ovarian tumors. Diagn Pathol 7:1-10.
136. Paige AJ, Brown R. 2008. Pharmaco(epi)genomics in ovarian cancer. Pharmacogenomics 9:1825-1834.
137. Payne C, Braun RE. 2006. Histone lysine trimethylation exhibits a distinct perinuclear distribution in Plzf-expressing spermatogonia. Dev Biol 293:461-472.
138. Petersen PH, Tang H, Zou K, Zhong W. 2006. The enigma of the numb-Notch relationship during mammalian embryogenesis. Dev Neurosci 28:156-168.
139. Pharoah PD, Palmieri RT, Ramus SJ, Gayther SA, Andrulis IL, Anton-Culver H, Antonenkova N, Antoniou AC, Goldgar D; BCFR Investigators, Beattie MS, Beckmann MW, Birrer MJ, Bogdanova N, Bolton KL, Brewster W, Brooks-Wilson A, Brown R, Butzow R, Caldes T, Caligo MA, Campbell I, Chang-Claude J, Chen YA, Cook LS, Couch FJ, Cramer DW, Cunningham JM, Despierre E, Doherty JA, Dörk T, Dürst M, Eccles DM, Ekici AB, Easton D; EMBRACE Investigators, Fasching PA, de Fazio A, Fenstermacher DA, Flanagan JM, Fridley BL, Friedman E, Gao B, Sinilnikova O; GEMO Study Collaborators, Gentry-Maharaj A, Godwin AK, Goode EL, Goodman MT, Gross J, Hansen TV, Harnett P, Rookus M; HEBON Investigators, Heikkinen T, Hein R, Høgdall C, Høgdall E, Iversen ES, Jakubowska A, Johnatty SE, Karlan BY, Kauff ND, Kaye SB, Chenevix-Trench G; kConFab Investigators and the Consortium of Investigators of Modifiers of BRCA1/2, Kelemen LE, Kiemeney LA, Kjaer SK, Lambrechts D, Lapolla JP, Lázaro C, Le ND, Leminen A, Leunen K, Levine DA, Lu Y, Lundvall L, Macgregor S, Marees T, Massuger LF, McLaughlin JR, Menon U, Montagna M, Moysich KB, Narod SA, Nathanson KL, Nedergaard L, Ness RB, Nevanlinna H, Nickels S, Osorio A, Paul J, Pearce CL, Phelan CM, Pike MC, Radice P, Rossing MA, Schildkraut JM, Sellers TA, Singer CF, Song H, Stram DO, Sutphen R, Lindblom A; SWE-BRCA Investigators, Terry KL, Tsai YY, van Altena AM, Vergote I, Vierkant RA, Vitonis AF, Walsh C, Wang-Gohrke S, Wappenschmidt B, Wu AH, Ziogas A, Berchuck A, Risch HA; Ovarian Cancer Association Consortium. 2011. The role of KRAS rs61764370 in invasive epithelial ovarian cancer: Implications for clinical testing. Clin Cancer Res 17:3742-3750.
140. Pilarski R, Patel DA, Weitzel J, McVeigh T, Dorairaj JJ, Heneghan HM, Miller N, Weidhaas JB, Kerin MJ, McKenna M, Wu X, Hildebrandt M, Zelterman D, Sand S, Shulman LP. 2012. The KRAS-variant is associated with risk of developing double primary breast and ovarian cancer. PLoS ONE 7:1-5.
141. Pirola L, Zerzaihi O, Vidal H, Solari F. 2012. Protein acetylation mechanisms in the regulation of insulin and insulin-like growth factor 1 signalling. Mol Cell Endocrinol 362:1-10.
142. Plisiecka-Halasa J, Karpinska G, Szymanska T, Ziolkowska I, Madry R, Timorek A, Debniak J, Ulanska M, Jedryka M, Chudecka-Glaz A, Klimek M, Rembiszewska A, Kraszewska E, Dybowski B, Markowska J, Emerich J, Pluzanska A, Goluda M, Rzepka-Gorska I, Urbanski K, Zielinski J, Stelmachow J, Chrabowska M, Kupryjanczyk J. 2003. P21WAF1, P27KIP1, TP53 and C-MYC analysis in 204 ovarian carcinomas treated with platinum-based regimens. Ann Oncol 14:1078-1085.
143. Powell SN, Kachnic LA. 2003. Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation. Oncogene 22:5784-5791.
144. Pratt EB, Wentzell JS, Maxson JE, Courter L, Hazelett D, Christian JL. 2011. The cell giveth and the cell taketh away: An overview of Notch pathway activation by endocytic trafficking of ligands and receptors. Acta Histochem 113:248-255.
145. Psyrri A, Bamias A, Yu Z, Weinberger PM, Kassar M, Markakis S, Kowalski D, Efstathiou E, Camp RL, Rimm DL, Dimopoulos MA. 2005. Subcellular localization and protein levels of cyclin-dependent kinase inhibitor p27 independently predict for survival in epithelial ovarian cancer. Clin Cancer Res 11:8384-8390.
146. Ramirez PT, Gershenson DM, Tortolero-Luna G, Ramondetta LM, Fightmaster D, Wharton JT, Wolf JK. 2001. Expression of cell-cycle mediators in ovarian cancer cells after transfection with p16(INK4a), p21(WAF1/Cip-1), and p53. Gynecol Oncol 83:543-548.
147. Ratner E, Lu L, Boeke M, Barnett R, Nallur S, Chin LJ, Pelletier C, Blitzblau R, Tassi R, Paranjape T, Hui P, Godwin AK, Yu H, Risch H, Rutherford T, Schwartz P, Santin A, Matloff E, Zelterman D, Slack FJ, Weidhaas JB. 2010. A KRAS-variant in ovarian cancer acts as a genetic marker of cancer risk. Cancer Res 70:6509-6515.
148. Ratner ES, Keane FK, Lindner R, Tassi RA, Paranjape T, Glasgow M, et al. 2012. A KRAS variant is a biomarker of poor outcome, platinum chemotherapy resistance and a potential target for therapy in ovarian cancer. Oncogene 31:4559-4566.
149. Ray A, Meng E, Reed E, Shevde LA, Rocconi RP. 2011. Hedgehog signaling pathway regulates the growth of ovarian cancer spheroid forming cells. Int J Oncol 39:797-804.
150. Reles A, Wen WH, Schmider A, Gee C, Runnebaum IB, Kilian U, Jones LA, El-Naggar A, Minguillon C, Schonborn I, Reich O, Kreienberg R, Lichtenegger W, Press MF. 2001. Correlation of p53 mutations with resistance to platinum-based chemotherapy and shortened survival in ovarian cancer. Clin Cancer Res 7:2984-2997.
151. Reynaud-Deonauth S, Zhang H, Afouda A, Taillefert S, Beatus P, Kloc M, Etkin LD, Fischer-Lougheed J, Spohr G. 2002. Notch signaling is involved in the regulation of Id3 gene transcription during Xenopus embryogenesis. Differentiation 69:198-208.
152. Rose SL, Robertson AD, Goodheart MJ, Smith BJ, DeYoung BR, Buller RE. 2003. The impact of p53 protein core domain structural alteration on ovarian cancer survival. Clin Cancer Res 9:4139-4144.
153. Sabol M, Car D, Musani V, Ozretic P, Oreskovic S, Weber I, Levanat S. 2012. The Hedgehog signaling pathway in ovarian teratoma is stimulated by Sonic Hedgehog which induces internalization of patched. Int J Oncol 41:1411-1418.
154. Saga Y, Mizukami H, Suzuki M, Kohno T, Urabe M, Ozawa K, Sato I. 2002. Overexpression of PTEN increases sensitivity to SN-38, an active metabolite of the topoisomerase I inhibitor irinotecan, in ovarian cancer cells. Clin Cancer Res 8:1248-1252.
155. Sagarra RA, Andrade LA, Martinez EZ, Pinto GA, Syrjanen KJ, Derchain SF. 2002. P53 and Bcl-2 as prognostic predictors in epithelial ovarian cancer. Int J Gynecol Cancer 12:720-727.
156. Saldanha SN, Tollefsbol TO. 2012. The role of nutraceuticals in chemoprevention and chemotherapy and their clinical outcomes. J Oncol 2012:192464.
157. Sandhu C, Donovan J, Bhattacharya N, Stampfer M, Worland P, Slingerland J. 2000. Reduction of Cdc25A contributes to cyclin E1-Cdk2 inhibition at senescence in human mammary epithelial cells. Oncogene 19:5314-5323.
158. Sarkar FH, Li Y, Wang Z, Kong D. 2010. The role of nutraceuticals in the regulation of Wnt and Hedgehog signaling in cancer. Cancer Metastasis Rev 29:383-394.
159. Sarojini S, Tamir A, Lim H, Li S, Zhang S, Goy A, Pecora A, Suh KS. 2012. Early detection biomarkers for ovarian cancer. J Oncol 2012:1-15.
160. Sasaki Y, Ishida S, Morimoto I, Yamashita T, Kojima T, Kihara C, Tanaka T, Imai K, Nakamura Y, Tokino T. 2002. The p53 family member genes are involved in the Notch signal pathway. J Biol Chem 277:719-724.
161. Schmider-Ross A, Pirsig O, Gottschalk E, Denkert C, Lichtenegger W, Reles A. 2006. Cyclin-dependent kinase inhibitors CIP1 (p21) and KIP1 (p27) in ovarian cancer. J Cancer Res Clin Oncol 132:163-170.
162. Schreck KC, Taylor P, Marchionni L, Gopalakrishnan V, Bar EE, Gaiano N, Eberhart CG. 2010. The Notch target Hes1 directly modulates Gli1 expression and Hedgehog signaling: A potential mechanism of therapeutic resistance. Clin Cancer Res 16:6060-6070.
163. Schuyer M, van der Burg ME, Henzen-Logmans SC, Fieret JH, Klijn JG, Look MP, Foekens JA, Stoter G, Berns EM. 2001. Reduced expression of BAX is associated with poor prognosis in patients with epithelial ovarian cancer: A multifactorial analysis of TP53, p21, BAX and BCL-2. Br J Cancer 85:1359-1367.
164. Scoumanne A, Chen X. 2008. Protein methylation: A new mechanism of p53 tumor suppressor regulation. Histol Histopathol 23:1143-1149.
165. Scully RE. 1995. Early de novo ovarian cancer and cancer developing in benign ovarian lesions. Int J Gynaecol Obstet 49:S9-S15.
166. Seeber LM, van Diest PJ. 2012. Epigenetics in ovarian cancer. Methods Mol Biol 863:253-269.
167. Semaan A, Qazi AM, Seward S, Chamala S, Bryant CS, Kumar S, Morris R, Steffes CP, Bouwman DL, Munkarah AR, Weaver DW, Gruber SA, Batchu RB. 2011. MicroRNA-101 inhibits growth of epithelial ovarian cancer by relieving chromatin-mediated transcriptional repression of p21(waf(1)/cip(1)). Pharm Res 28:3079-3090.
168. Sherr CJ. 1996. Cancer cell cycles. Science 274:1672-1677.
169. Shigemasa K, Tanimoto H, Parham GP, Parmley TH, Ohama K, O'Brien TJ. 1999. Cyclin D1 overexpression and p53 mutation status in epithelial ovarian cancer. J Soc Gynecol Investig 6:102-108.
170. Shigemasa K, Shiroyama Y, Sawasaki T, Fujii T, Nagai N, Parmley TH, O'Brien TJ, Ohama K. 2001. Underexpression of cyclin-dependent kinase inhibitor p27 is associated with poor prognosis in serous ovarian carcinomas. Int J Oncol 18:953-958.
171. Shin DM, Shaffer DJ, Wang H, Roopenian DC, Morse HC, III. 2008. NOTCH is part of the transcriptional network regulating cell growth and survival in mouse plasmacytomas. Cancer Res 68:9202-9211.
172. Sims-Mourtada J, Izzo JG, Ajani J, Chao KS. 2007. Sonic Hedgehog promotes multiple drug resistance by regulation of drug transport. Oncogene 26:5674-5679.
173. Skirnisdottir I, Seidal T, Gerdin E, Sorbe B. 2002. The prognostic importance of p53, bcl-2, and bax in early stage epithelial ovarian carcinoma treated with adjuvant chemotherapy. Int J Gynecol Cancer 12:265-276.
174. Smeenk L, van Heeringen SJ, Koeppel M, Gilbert B, Janssen-Megens E, Stunnenberg HG, Lohrum M. 2011. Role of p53 serine 46 in p53 target gene regulation. PLoS ONE 6:1-14.
175. Smith V, Hobbs S, Court W, Eccles S, Workman P, Kelland LR. 2002. ErbB2 overexpression in an ovarian cancer cell line confers sensitivity to the HSP90 inhibitor geldanamycin. Anticancer Res 22:1993-1999.
176. Smolle E, Taucher V, Pichler M, Petru E, Lax S, Haybaeck J. 2013. Targeting signaling pathways in epithelial ovarian cancer. Int J Mol Sci 14:9536-9555.
177. Sobinoff AP, Mahony M, Nixon B, Roman SD, McLaughlin EA. 2011. Understanding the Villain: DMBA-induced preantral ovotoxicity involves selective follicular destruction and primordial follicle activation through PI3K/Akt and mTOR signaling. Toxicol Sci 123:563-575.
178. Song Z, Yue W, Wei B, Wang N, Li T, Guan L, Shi S, Zeng Q, Pei X, Chen L. 2011. Sonic hedgehog pathway is essential for maintenance of cancer stem-like cells in human gastric cancer. PLoS ONE 6:1-13.
179. Song T, Kim MK, Lee YY, Choi CH, Kim TJ, Lee JW, Kim BG, Bae DS. 2013. Phase II study of ifosfamide and cisplatin for the treatment of recurrent ovarian cancer. Cancer Chemother Pharmacol 72:653-660.
180. Soto-Reyes E, Recillas-Targa F. 2010. Epigenetic regulation of the human p53 gene promoter by the CTCF transcription factor in transformed cell lines. Oncogene 29:2217-2227.
181. Spellman PT, et al., Cancer Genome Atlas Research Network. 2011. Integrated genomic analyses of ovarian carcinoma. Nature 474:609-615.
182. Stathopoulos GP, Papadimitriou C, Aravantinos G, Rigatos SK, Malamos N, Stathopoulos JG, Kaparelou M, Koutantos J, Andreadis C. 2012. Maintenance chemotherapy or not in ovarian cancer stages IIIA, B, C, and IV after disease recurrence. J BUON 17:735-739.
183. Steffensen KD, Alvero AB, Yang Y, Waldstrom M, Hui P, Holmberg JC, Silasi DA, Jakobsen A, Rutherford T, Mor G. 2011a. Prevalence of epithelial ovarian cancer stem cells correlates with recurrence in early-stage ovarian cancer. J Oncol 2011:620523.
184. Steffensen KD, Waldstrom M, Grove A, Lund B, Pallisgard N, Jakobsen A. 2011b. Improved classification of epithelial ovarian cancer: Results of 3 danish cohorts. Int J Gynecol Cancer 21:1592-1600.
185. Steg A, Wang W, Blanquicett C, Grunda JM, Eltoum IA, Wang K, Buchsbaum DJ, Vickers SM, Russo S, Diasio RB, Frost AR, LoBuglio AF, Grizzle WE, Johnson MR. 2006. Multiple gene expression analyses in paraffin-embedded tissues by TaqMan low-density array: Application to hedgehog and Wnt pathway analysis in ovarian endometrioid adenocarcinoma. J Mol Diagn 8:76-83.
186. Stewart CJ, Leung Y, Walsh MD, Walters RJ, Young JP, Buchanan DD. 2012. KRAS mutations in ovarian low-grade endometrioid adenocarcinoma: Association with concurrent endometriosis. Hum Pathol 43:1177-1183.
187. Stocker H, Andjelkovic M, Oldham S, Laffargue M, Wymann MP, Hemmings BA, Hafen E. 2002. Living with lethal PIP3 levels: Viability of flies lacking PTEN restored by a PH domain mutation in Akt/PKB. Science 295:2088-2091.
188. Szabova L, Yin C, Bupp S, Guerin TM, Schlomer JJ, Householder DB, Baran ML, Yi M, Song Y, Sun W, McDunn JE, Martin PL, Van Dyke T, Difilippantonio S. 2012. Perturbation of Rb, p53, and Brca1 or Brca2 cooperate in inducing metastatic serous epithelial ovarian cancer. Cancer Res 72:4141-4153.
189. Tai YT, Lee S, Niloff E, Weisman C, Strobel T, Cannistra SA. 1998. BAX protein expression and clinical outcome in epithelial ovarian cancer. J Clin Oncol 16:2583-2590.
190. Takayama G, Ohtani M, Minowa A, Matsuda S, Koyasu S. 2012. Class I PI3K-mediated Akt and ERK signals play a critical role in Fc{varepsilon}RI-induced degranulation in mast cells. Int Immunol 25:215-220.
191. Tam KF, Liu VW, Liu SS, Tsang PC, Cheung AN, Yip AM, Ngan HY. 2007. Methylation profile in benign, borderline and malignant ovarian tumors. J Cancer Res Clin Oncol 133:331-341.
192. Teixeira J, Rueda BR, Pru JK. 2008. Uterine stem cells. Girard L, editor. StemBook. Cambridge (MA).
193. Todd MC, Sclafani RA, Langan TA. 2000. Ovarian cancer cells that coexpress endogenous Rb and p16 are insensitive to overexpression of functional p16 protein. Oncogene 19:258-264.
194. Tutt A, Ashworth A. 2002. The relationship between the roles of BRCA genes in DNA repair and cancer predisposition. Trends Mol Med 8:571-576.
195. Urick ME, Rudd ML, Godwin AK, Sgroi D, Merino M, Bell DW. 2011. PIK3R1 (p85alpha) is somatically mutated at high frequency in primary endometrial cancer. Cancer Res 71:4061-4067.
196. Usha L, Sill MW, Darcy KM, Benbrook DM, Hurteau JA, Michelin DP, Mannel RS, Hanjani P, De Geest K, Godwin AK. 2011. A Gynecologic Oncology Group phase II trial of the protein kinase C-beta inhibitor, enzastaurin and evaluation of markers with potential predictive and prognostic value in persistent or recurrent epithelial ovarian and primary peritoneal malignancies. Gynecol Oncol 121:455-461.
197. Vereczkey I, Serester O, Dobos J, Gallai M, Szakacs O, Szentirmay Z, Toth E. 2011. Molecular characterization of 103 ovarian serous and mucinous tumors. Pathol Oncol Res 17:551-559.
198. Vikhanskaya F, Erba E, D'Incalci M, Broggini M. 1996. Changes in cyclins and cyclin-dependent kinases induced by DNA damaging agents in a human ovarian cancer cell line expressing mutated or wild-type P53. Exp Cell Res 227:380-385.
199. Wang X, Fu Y, Chen X, Ye J, Lu B, Ye F, Lu W, Xie X. 2010a. The expressions of bHLH gene HES1 and HES5 in advanced ovarian serous adenocarcinomas and their prognostic significance: A retrospective clinical study. J Cancer Res Clin Oncol 136:989-996.
200. Wang YQ, Zhang JR, Li SD, He YY, Yang YX, Liu XL, Wan XP. 2010b. Aberrant methylation of breast and ovarian cancer susceptibility gene 1 in chemosensitive human ovarian cancer cells does not involve the phosphatidylinositol 3′-kinase-Akt pathway. Cancer Sci 101:1618-1623.
201. Wang QE, Milum K, Han C, Huang YW, Wani G, Thomale J, Wani AA. 2011. Differential contributory roles of nucleotide excision and homologous recombination repair for enhancing cisplatin sensitivity in human ovarian cancer cells. Mol Cancer 10:1-12.
202. Weberpals JI, Clark-Knowles KV, Vanderhyden BC. 2008. Sporadic epithelial ovarian cancer: Clinical relevance of BRCA1 inhibition in the DNA damage and repair pathway. J Clin Oncol 26:3259-3267.
203. Weberpals JI, Tu D, Squire JA, Amin MS, Islam S, Pelletier LB, O'Brien AM, Hoskins PJ, Eisenhauer EA. 2011. Breast cancer 1 (BRCA1) protein expression as a prognostic marker in sporadic epithelial ovarian carcinoma: An NCIC CTG OV.16 correlative study. Ann Oncol 22:2403-2410.
204. Weidhaas JB, Slack FJ. 2011. KRAS rs61764370 in epithelial ovarian cancer-letter. Clin Cancer Res 17:1-2.
205. Wiltshire T, Senft J, Wang Y, Konat GW, Wenger SL, Reed E, Wang W. 2007. BRCA1 contributes to cell cycle arrest and chemoresistance in response to the anticancer agent irofulven. Mol Pharmacol 71:1051-1060.
206. Wysham WZ, Mhawech-Fauceglia P, Li H, Hays L, Syriac S, Skrepnik T, Wright J, Pande N, Hoatlin M, Pejovic T. 2012. BRCAness profile of sporadic ovarian cancer predicts disease recurrence. PLoS ONE 7:1-7.
207. Xu G, Zhang W, Bertram P, Zheng XF, McLeod H. 2004. Pharmacogenomic profiling of the PI3K/PTEN-AKT-mTOR pathway in common human tumors. Int J Oncol 24:893-900.
208. Xu CX, Xu M, Tan L, Yang H, Permuth-Wey J, Kruk PA, Wenham RM, Nicosia SV, Lancaster JM, Sellers TA, Cheng JQ. 2012a. MicroRNA miR-214 regulates ovarian cancer cell stemness by targeting p53/Nanog. J Biol Chem 287:34970-34978.
209. Xu X, Dong Z, Yang Y, Yuan Z, Qu X, Kong B. 2012b. The upregulation of signal transducer and activator of transcription 5-dependent microRNA-182 and microRNA-96 promotes ovarian cancer cell proliferation by targeting forkhead box O3 upon leptin stimulation. Int J Biochem Cell Biol 45:536-545.
210. Yamaguchi E, Chiba S, Kumano K, Kunisato A, Takahashi T, Takahashi T, Hirai H. 2002. Expression of Notch ligands, Jagged1, 2 and Delta1 in antigen presenting cells in mice. Immunol Lett 81:59-64.
211. Yamamoto S, Tsuda H, Takano M, Iwaya K, Tamai S, Matsubara O. 2011. PIK3CA mutation is an early event in the development of endometriosis-associated ovarian clear cell adenocarcinoma. J Pathol 225:189-194.
212. Yan X, Fraser M, Qiu Q, Tsang BK. 2006. Over-expression of PTEN sensitizes human ovarian cancer cells to cisplatin-induced apoptosis in a p53-dependent manner. Gynecol Oncol 102:348-355.
213. Yang HJ, Liu VW, Wang Y, Tsang PC, Ngan HY. 2006. Differential DNA methylation profiles in gynecological cancers and correlation with clinico-pathological data. BMC Cancer 6:1-10.
214. Yang H, Kong W, He L, Zhao JJ, O'Donnell JD, Wang J, Wenham RM, Coppola D, Kruk PA, Nicosia SV, Cheng JQ. 2008. MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res 68:425-433.
215. Yang C, Chen H, Yu L, Shan L, Xie L, Hu J, Chen T, Tan Y. 2013. Inhibition of FOXM1 transcription factor suppresses cell proliferation and tumor growth of breast cancer. Cancer Gene Ther 20:117-124.
216. Yemelyanova A, Vang R, Kshirsagar M, Lu D, Marks MA, Shih Ie M, Kurman RJ. 2011. Immunohistochemical staining patterns of p53 can serve as a surrogate marker for TP53 mutations in ovarian carcinoma: An immunohistochemical and nucleotide sequencing analysis. Mod Pathol 24:1248-1253.
217. Zhang H, Somasundaram K, Peng Y, Tian H, Zhang H, Bi D, Weber BL, El-Deiry WS. 1998. BRCA1 physically associates with p53 and stimulates its transcriptional activity. Oncogene 16:1713-1721.
218. Zhang X, Wen H, Shi X. 2012. Lysine methylation: Beyond histones. Acta Biochim Biophys Sin (Shanghai) 44:14-27.
219. Zhou L, Graves M, Macdonald G, Cipollone J, Mueller CR, Roskelley CD. 2013. Microenvironmental regulation of BRCA1 gene expression by c-Jun and Fra2 in pre-malignant human ovarian surface epithelial cells. Mol Cancer Res 11:272-281.
220. Zikan M, Janatova M, Pavlista D, Pohlreich P. 2007. High frequency of BRCA1/2 and p53 somatic inactivation in sporadic ovarian cancer. J Genet 86:169-171.
221. Zikan M, Pohlreich P, Freitag P, Janousek M, Pavlista D, Fischerova D, Jancarkova N, Slama J, Pinkavova I, Cibula D. 2008. Inactivation of BRCA1, BRCA2 and p53 genes in sporadic ovarian cancer. Ceska Gynekol 73:298-302.
222. Ziolkowska-Seta I, Madry R, Kraszewska E, Szymanska T, Timorek A, Rembiszewska A, Kupryjanczyk J. 2009. TP53, BCL-2 and BAX analysis in 199 ovarian cancer patients treated with taxane-platinum regimens. Gynecol Oncol 112:179-184.
223. Zweemer RP, Shaw PA, Verheijen RM, Ryan A, Berchuck A, Ponder BA, Risch H, McLaughlin JR, Narod SA, Menko FH, Kenemans P, Jacobs IJ. 1999. Accumulation of p53 protein is frequent in ovarian cancers associated with BRCA1 and BRCA2 germline mutations. J Clin Pathol 52:372-375.