Interference with ER-α enhances the therapeutic efficacy of the selective CDK inhibitor roscovitine towards ER-positive breast cancer cells

Journal of Cellular Biochemistry

Volumn 112, Issue 4, 2011, Pages 1103-1117

  Wȩsierska Ga̧dek, Józefa ^a   Gritsch, David ^a   Zulehner, Nora ^a   Komina, Oxana ^a   Maurer, Margarita ^a  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

Activation of wt p53; Anti estrogen; Cell Cycle; ER activation; Estrogen; G2 arrest; P Ser118 ER ; SERMs; Transcriptional elongation

Indexed keywords

CYCLIN DEPENDENT KINASE 2; CYCLIN DEPENDENT KINASE 7; ESTROGEN RECEPTOR ALPHA; PROTEIN P53; RNA POLYMERASE II; ROSCOVITINE; TAMOXIFEN;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CANCER; CANCER CELL CULTURE; CARBOXY TERMINAL SEQUENCE; CELL CYCLE ARREST; CELL CYCLE PROGRESSION; CELL STRAIN MCF 7; CONTROLLED STUDY; DOWN REGULATION; DRUG EFFICACY; DRUG POTENTIATION; ENZYME INHIBITION; HUMAN; HUMAN CELL; MITOCHONDRIAL MEMBRANE POTENTIAL; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION;

BREAST NEOPLASMS; CELL CYCLE; CELL LINE, TUMOR; CELL PROLIFERATION; CYCLIN-DEPENDENT KINASE 2; CYCLIN-DEPENDENT KINASES; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG SYNERGISM; ESTROGEN RECEPTOR ALPHA; FLOW CYTOMETRY; G2 PHASE; HELA CELLS; HUMANS; IMMUNOBLOTTING; MEMBRANE POTENTIAL, MITOCHONDRIAL; PHOSPHORYLATION; PROTEIN KINASE INHIBITORS; PURINES; SELECTIVE ESTROGEN RECEPTOR MODULATORS; SERINE; TAMOXIFEN; TIME FACTORS;

EID: 79952552455     PISSN: 07302312     EISSN: 10974644     Source Type: Journal    
DOI: 10.1002/jcb.23024     Document Type: Article

References (102)

1. Ali S, Metzger D, Bornert JM, Chambon P. 1993. Modulation of transcriptional activation by ligand-dependent phosphorylation of the human oestrogen receptor A/B region. EMBO J 12:1153-1160. (Pubitemid 23095864)
2. Alvi AJ, Austen B, Weston VJ, Fegan C, MacCallum D, Gianella-Borradori A, Lane DP, Hubank M, Powell JE, Wei W, Taylor AM, Moss PA, Stankovic T. 2005. A novel CDK inhibitor, CYC202 (R-roscovitine), overcomes the defect in p53-dependent apoptosis in B-CLL by down-regulation of genes involved in transcription regulation and survival. Blood 105:4484-4491. (Pubitemid 40720798)
3. Angeloni SV, Martin MB, Garcia-Morales P, Castro-Galache MD, Ferragut JA, Saceda M. 2004. Regulation of estrogen receptor-alpha expression by the tumor suppressor gene p53 in MCF-7 cells. J Endocrinol 180:497-504. (Pubitemid 38443401)
4. Arnold A, Papanikolaou A. 2005. Cyclin D1 in breast cancer pathogenesis. J Clin Oncol 23:4215-4224. (Pubitemid 46211327)
5. Aronica SM, Katzenellenbogen BS. 1993. Stimulation of estrogen receptor-mediated transcription and alteration in the phosphorylation state of the rat uterine estrogen receptor by estrogen, cyclic adenosine monophosphate, and insulin-like growth factor-I. Mol Endocrinol 7:743-752. (Pubitemid 23207377)
6. Bartkova J, Lukas J, Muller H, Lutzhoft D, Strauss M, Bartek J. 1994. Cyclin D1 protein expression and function in human breast cancer. Int J Cancer 57:353-361. (Pubitemid 24168609)
7. Benson C, White J, De Bono J, O'Donnell A, Raynaud F, Cruickshank C, McGrath H, Walton M, Workman P, Kaye S, Cassidy J, Gianella-Borradori A, Judson I, Twelves C. 2007. A phase I trial of the selective oral cyclin-dependent kinase inhibitor seliciclib (CYC202; R-Roscovitine), administered twice daily for 7 days every 21 days. Br J Cancer 96:29-37. (Pubitemid 46094635)
8. Blagosklonny MV, Pardee AB. 2001. Exploiting cancer cell cycling for selective protection of normal cells. Cancer Res 61:4301-4305. (Pubitemid 32685747)
9. Bres V, Yoh SM, Jones KA. 2008. The multi-tasking P-TEFb complex. Curr Opin Cell Biol 20:334-340.
10. Brzozowski AM, Pike AC, Dauter Z, Hubbard RE, Bonn T, Engstrom O, Ohman L, Greene GL, Gustafsson JA, Carlquist M. 1997. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 389:753-758. (Pubitemid 27458965)
11. Chen D, Riedl T, Washbrook E, Pace PE, Coombes RC, Egly JM, Ali S. 2000. Activation of estrogen receptor alpha by S118 phosphorylation involves a ligand-dependent interaction with TFIIH and participation of CDK7. Mol Cell 6:127-137.
12. Cheskis BJ, Greger JG, Nagpal S, Freedman LP. 2007. Signaling by estrogens. J Cell Physiol 213:610-617. (Pubitemid 350058252)
13. Chou TC, Talalay P. 1984. Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 22:27-55.
14. Collaborative Group on Hormonal Factors in Breast Cancer. 1996. Breast cancer and hormonal contraceptives: Collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies. Lancet 347:1713-1727.
15. Core LJ, Lis JT. 2008. Transcription regulation through promoter-proximal pausing of RNA polymerase II. Science 319:1791-1792. (Pubitemid 351451556)
16. Couse JF, Korach KS. 1999. Estrogen receptor null mice: What have we learned and where will they lead us? Endocr Rev 20:358-417.
17. David-Pfeuty T. 1999. Potent inhibitors of cyclin-dependent kinase 2 induce nuclear accumulation of wild-type p53 and nucleolar fragmentation in human untransformed and tumor-derived cells. Oncogene 18:7409-7422. (Pubitemid 30035042)
18. De Azevedo WF, Leclerc S, Meijer L, Havlicek L, Strnad M, Kim SH. 1997. Inhibition of cyclin-dependent kinases by purine analogues: Crystal structure of human cdk2 complexed with roscovitine. Eur J Biochem 243:518-526. (Pubitemid 27060442)
19. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). 2005. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet 365: 1687-1717.
20. Enmark E, Gustafsson JA. 1999. Oestrogen receptors-An overview. J Intern Med 246:133-138.
21. Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE. 1994. Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet 343: 692-695. (Pubitemid 24087847)
22. Galimberti F, Thompson SL, Liu X, Li H, Memoli V, Green SR, DiRenzo J, Greninger P, Sharma SV, Settleman J, Compton DA, Dmitrovsky E. 2010. Targeting the cyclin E-Cdk-2 complex represses lung cancer growth by triggering anaphase catastrophe. Clin Cancer Res 16:109-120.
23. Galons H, Oumata N, Meijer L. 2010. Cyclin-dependent kinase inhibitors: A survey of recent patent literature. Expert Opin Ther Pat 20:377-404.
24. Glass AG, Lacey JV, Jr., Carreon JD, Hoover RN. 2007. Breast cancer incidence, 1980-2006: Combined roles of menopausal hormone therapy, screening mammography, and estrogen receptor status. J Natl Cancer Inst 99:1152-1161. (Pubitemid 47233065)
25. Gritsch D, Maurer M, Zulehner N, Wȩsierska-Ga̧dek J. 2011. Tamoxifen enhances the anti-proliferative effect of roscovitine, a selective cyclin-dependent kinase inhibitor, on human ER-positive human breast cancer cells. J Exp Therap Oncol 9:37-45.
26. Hahntow IN, Schneller F, Oelsner M, Weick K, Ringshausen I, Fend F, Peschel C, Decker T. 2004. Cyclin-dependent kinase inhibitor Roscovitine induces apoptosis in chronic lymphocytic leukemia cells. Leukemia 18: 747-755. (Pubitemid 38500193)
27. Hanahan D, Weinberg RA. 2000. The hallmarks of cancer. Cell 100:57-70. (Pubitemid 30046295)
28. Hartman J, Lam EW, Gustafsson JA, Strom A. 2009. Hes-6, an inhibitor of Hes-1, is regulated by 17beta-estradiol and promotes breast cancer cell proliferation. Breast Cancer Res 11:R79.
29. Harwell RM, Mull BB, Porter DC, Keyomarsi K. 2004. Activation of cyclin-dependent kinase 2 by full length and low molecular weight forms of cyclin E in breast cancer cells. J Biol Chem 279:12695-12705. (Pubitemid 38445841)
30. Havlicek L, Hanus J, Vesely J, Leclerc S, Meijer L, Shaw G, Strnad M. 1997. Cytokinin-derived cyclin-dependent kinase inhibitors: Synthesis and cdc2 inhibitory activity of olomoucine and related compounds. J Med Chem 40:408-412. (Pubitemid 27080019)
31. Hilakivi-Clarke L. 2000. Estrogens, BRCA1, and breast cancer. Cancer Res 60:4993-5001.
32. Hopp TA, Fuqua SA. 1998. Estrogen receptor variants. J Mammary Gland Biol Neoplasia 3:73-83. (Pubitemid 128513221)
33. Hulka BS, Stark AT. 1995. Breast cancer: Cause and prevention. Lancet 346:883-887.
34. Jazaeri O, Shupnik MA, Jazaeri AA, Rice LW. 1999. Expression of estrogen receptor alpha mRNA and protein variants in human endometrial carcinoma. Gynecol Oncol 74:38-47. (Pubitemid 29331165)
35. Joel PB, Traish AM, Lannigan DA. 1995. Estradiol and phorbol ester cause phosphorylation of serine 118 in the human estrogen receptor. Mol Endocrinol 9:1041-1052.
36. Joel PB, Traish AM, Lannigan DA. 1998. Estradiol-induced phosphorylation of serine 118 in the estrogen receptor is independent of p42/p44 mitogen-activated protein kinase. J Biol Chem 273:13317-13323. (Pubitemid 28246906)
37. Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, Masushige S, Gotoh Y, Nishida E, Kawashima H, Metzger D, Chambon P. 1995. Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science 270:1491-1494.
38. Katzenellenbogen JA, Katzenellenbogen BS. 1996. Nuclear hormone receptors: Ligand-activated regulators of transcription and diverse cell responses. Chem Biol 3:529-536. (Pubitemid 26324165)
39. Katzenellenbogen JA, O'Malley BW, Katzenellenbogen BS. 1996. Tripartite steroid hormone receptor pharmacology: Interaction with multiple effector sites as a basis for the cell- and promoter-specific action of these hormones. Mol Endocrinol 10:119-131. (Pubitemid 26042544)
40. Key TJ, Verkasalo PK. 1999. Endogenous hormones and the aetiology of breast cancer. Breast Cancer Res 1:18-21. (Pubitemid 32223530)
41. Key TJ, Verkasalo PK, Banks E. 2001. Epidemiology of breast cancer. Lancet Oncol 2:133-140. (Pubitemid 33585924)
42. Keyomarsi K, Conte D, Jr., Toyofuku W, Fox MP. 1995. Deregulation of cyclin E in breast cancer. Oncogene 11:941-950.
43. Konigsberg R, Rogelsperger O, Jager W, Thalhammer T, Klimpfinger M, De Santis M, Hudec M, Dittrich C. 2008. Cell cycle dysregulation influences survival in high risk breast cancer patients. Cancer Invest 26:734-740.
44. Kotala V, Uldrijan S, Horky M, Trbusek M, Strnad M, Vojtesek B. 2001. Potent induction of wild-type p53-dependent transcription in tumour cells by a synthetic inhibitor of cyclin-dependent kinases. Cell Mol Life Sci 58:1333-1339. (Pubitemid 32844102)
45. Kovar H, Jug G, Printz D, Bartl S, Schmid G, Wesierska-Gadek J. 2000. Characterization of distinct consecutive phases in non-genotoxic p53-induced apoptosis of Ewing tumor cells and the rate-limiting role of caspase 8. Oncogene 19:4096-4107.
46. Lannigan DA. 2003. Estrogen receptor phosphorylation. Steroids 68:1-9. (Pubitemid 35418300)
47. Lapenna S, Giordano A. 2009. Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov 8:547-566.
48. Le Goff P, Montano MM, Schodin DJ, Katzenellenbogen BS. 1994. Phosphorylation of the human estrogen receptor. Identification of hormone-regulated sites and examination of their influence on transcriptional activity. J Biol Chem 269:4458-4466.
49. Magnusson CM, Persson IR, Baron JA, Ekbom A, Bergstrom R, Adami HO. 1999. The role of reproductive factors and use of oral contraceptives in the aetiology of breast cancer in women aged 50 to 74 years. Int J Cancer 80: 231-236. (Pubitemid 29001726)
50. Malumbres M, Barbacid M. 2009. Cell cycle, CDKs and cancer: A changing paradigm. Nat Rev Cancer 9:153-166.
51. Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, Evans RM. 1995. The nuclear receptor superfamily: The second decade. Cell 83:835-839.
52. Matthews J, Gustafsson JA. 2003. Estrogen signaling: A subtle balance between ER alpha and ER beta. Mol Interv 3:281-292.
53. McClue SJ, Blake D, Clarke R, Cowan A, Cummings L, Fischer PM, MacKenzie M, Melville J, Stewart K, Wang S, Zhelev N, Zheleva D, Lane DP. 2002. In vitro and in vivo antitumor properties of the cyclin dependent kinase inhibitor CYC202 (R-roscovitine). Int J Cancer 102:463-468.
54. Meijer L, Borgne A, Mulner O, Chong JP, Blow JJ, Inagaki N, Inagaki M, Delcros JG, Moulinoux JP. 1997. Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur J Biochem 243:527-536. (Pubitemid 27060443)
55. Murphy CG, Fornier M. 2010. HER2-positive breast cancer: Beyond trastuzumab. Oncology (Williston Park) 24:410-415.
56. Murphy LC, Skliris GP, Rowan BG, Al-Dhaheri M, Williams C, Penner C, Troup S, Begic S, Parisien M, Watson PH. 2009. The relevance of phosphorylated forms of estrogen receptor in human breast cancer in vivo. J Steroid Biochem Mol Biol 114:90-95.
57. Murray CJ, Lopez AD. 1997. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet 349: 1498-1504. (Pubitemid 27216360)
58. Nass SJ, Dickson RB. 1997. Defining a role for c-Myc in breast tumorigenesis. Breast Cancer Res Treat 44:1-22. (Pubitemid 27179765)
59. Nathanson KL, Wooster R, Weber BL. 2001. Breast cancer genetics: What we know and what we need. Nat Med 7:552-556. (Pubitemid 32448321)
60. Negrini S, Gorgoulis VG, Halazonetis TD. 2010. Genomic instability-An evolving hallmark of cancer. Nat Rev Mol Cell Biol 11:220-228.
61. Oda K, Arakawa H, Tanaka T, Matsuda K, Tanikawa C, Mori T, Nishimori H, Tamai K, Tokino T, Nakamura Y, Taya Y. 2000. p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53. Cell 102:849-862.
62. Peto J, Collins N, Barfoot R, Seal S, Warren W, Rahman N, Easton DF, Evans C, Deacon J, Stratton MR. 1999. Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Natl Cancer Inst 91:943-949. (Pubitemid 29272520)
63. Reers M, Smith TW, Chen LB. 1991. J-aggregate formation of a carbocyanine as a quantitative fluorescent indicator of membrane potential. Biochemistry 30:4480-4486.
64. Rizzolio F, Tuccinardi T, Caligiuri I, Lucchetti C, Giordano A. 2010. CDK inhibitors: From the bench to clinical trials. Curr Drug Targets 11:279-290.
65. Rogalinska M, Blonski JZ, Komina O, Goralski P, Zolnierczyk JD, Piekarski H, Robak T, Kilianska ZM, Wesierska-Gadek J. 2010. R-roscovitine (Seliciclib) affects CLL cells more strongly than combinations of fludarabine or cladribine with cyclophosphamide: Inhibition of CDK7 sensitizes leukemic cells to caspase-dependent apoptosis. J Cell Biochem 109:217-235.
66. Ross RK, Paganini-Hill A, Wan PC, Pike MC. 2000. Effect of hormone replacement therapy on breast cancer risk: Estrogen versus estrogen plus progestin. J Natl Cancer Inst 92:328-332. (Pubitemid 30117736)
67. Russo J, Russo IH. 2006. The role of estrogen in the initiation of breast cancer. J Steroid Biochem Mol Biol 102:89-96. (Pubitemid 44750629)
68. Russo J, Russo IH. 2008. Breast development, hormones and cancer. Adv Exp Med Biol 630:52-56.
69. Russo J, Fernandez SV, Russo PA, Fernbaugh R, Sheriff FS, Lareef HM, Garber J, Russo IH. 2006. 17-Beta-estradiol induces transformation and tumorigenesis in human breast epithelial cells. FASEB J 20:1622-1634. (Pubitemid 44943799)
70. Sabbah M, Courilleau D, Mester J, Redeuilh G. 1999. Estrogen induction of the cyclin D1 promoter: Involvement of a cAMP response-like element. Proc Natl Acad Sci USA 96:11217-11222. (Pubitemid 29487361)
71. Schuuring E, Verhoeven E, Mooi WJ, Michalides RJ. 1992. Identification and cloning of two overexpressed genes, U21B31/PRAD1 and EMS1, within the amplified chromosome 11q13 region in human carcinomas. Oncogene 7:355-361.
72. Senderowicz AM. 2001. Cyclin-dependent kinase modulators: A novel class of cell cycle regulators for cancer therapy. Cancer Chemother Biol Response Modif 19:165-188.
73. Senderowicz AM. 2003. Small-molecule cyclin-dependent kinase modulators. Oncogene 22:6609-6620. (Pubitemid 37372341)
74. Sherr CJ, Roberts JM. 1999. CDK inhibitors: Positive and negative regulators of G1-phase progression. Genes Dev 13:1501-1512. (Pubitemid 29297917)
75. Sicinski P, Donaher JL, Parker SB, Li T, Fazeli A, Gardner H, Haslam SZ, Bronson RT, Elledge SJ, Weinberg RA. 1995. Cyclin D1 provides a link between development and oncogenesis in the retina and breast. Cell 82:621-630.
76. Spizzo R, Nicoloso MS, Lupini L, Lu Y, Fogarty J, Rossi S, Zagatti B, Fabbri M, Veronese A, Liu X, Davuluri R, Croce CM, Mills G, Negrini M, Calin GA. 2010. miR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor-alpha in human breast cancer cells. Cell Death Differ 17:246-254.
77. Spruck CH, Won KA, Reed SI. 1999. Deregulated cyclin E induces chromosome instability. Nature 401:297-300.
78. Sutherland RL, Musgrove EA. 2004. Cyclins and breast cancer. J Mammary Gland Biol Neoplasia 9:95-104. (Pubitemid 39137499)
79. Sutherland RL, Musgrove EA. 2009. CDK inhibitors as potential breast cancer therapeutics: New evidence for enhanced efficacy in ER+ disease. Breast Cancer Res 11:112.
80. te Poele RH, Okorokov AL, Joel SP. 1999. RNA synthesis block by 5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) triggers p53-dependent apoptosis in human colon carcinoma cells. Oncogene 18:5765-5772.
81. Vesely J, Havlicek L, Strnad M, Blow JJ, Donella-Deana A, Pinna L, Letham DS, Kato J, Detivaud L, Leclerc S, Meijer L. 1994. Inhibition of cyclin-dependent kinases by purine analogues. Eur J Biochem 224:771-786. (Pubitemid 24282865)
82. Vindelov LL. 1977. Flow microfluorometric analysis of nuclear DNA in cells from solid tumors and cell suspensions. A new method for rapid isolation and straining of nuclei. Virchows Arch B Cell Pathol 24:227-242.
83. Wakeling AE, Dukes M, Bowler J. 1991. A potent specific pure antiestrogen with clinical potential. Cancer Res 51:3867-3873.
84. Walter P, Green S, Greene G, Krust A, Bornert JM, Jeltsch JM, Staub A, Jensen E, Scrace G, Waterfield M. et al. 1985. Cloning of the human estrogen receptor cDNA. Proc Natl Acad Sci USA 82:7889-7893. (Pubitemid 16179869)
85. Washburn T, Hocutt A, Brautigan DL, Korach KS. 1991. Uterine estrogen receptor in vivo: Phosphorylation of nuclear specific forms on serine residues. Mol Endocrinol 5:235-242. (Pubitemid 21923687)
86. Weisz A, Basile W, Scafoglio C, Altucci L, Bresciani F, Facchiano A, Sismondi P, Cicatiello L, De Bortoli M. 2004. Molecular identification of ERalpha-positive breast cancer cells by the expression profile of an intrinsic set of estrogen regulated genes. J Cell Physiol 200:440-450. (Pubitemid 39006936)
87. Wesierska-Gadek J, Schmid G. 2000. Overexpressed poly(ADP-ribose) polymerase delays the release of rat cells from p53-mediated G(1) checkpoint. J Cell Biochem 80:85-103.
88. Wesierska-Gadek J, Schmid G. 2006. Dual action of the inhibitors of cyclin-dependent kinases: Targeting of the cell-cycle progression and activation of wild-type p53 protein. Expert Opin Investig Drugs 15:23-38. (Pubitemid 43034149)
89. Wesierska-Gadek J, Bohrn E, Herceg Z, Wang ZQ, Wurzer G. 2000. Differential susceptibility of normal and PARP knock-out mouse fibroblasts to proteasome inhibitors. J Cell Biochem 78:681-696. (Pubitemid 30620713)
90. Wesierska-Gadek J, Schloffer D, Kotala V, Horky M. 2002. Escape of p53 protein from E6-mediated degradation in HeLa cells after cisplatin therapy. Int J Cancer 101:128-136. (Pubitemid 34970904)
91. Wesierska-Gadek J, Schloffer D, Gueorguieva M, Uhl M, Skladanowski A. 2004. Increased susceptibility of poly(ADP-ribose) polymerase-1 knockout cells to antitumor triazoloacridone C-1305 is associated with permanent G2 cell cycle arrest. Cancer Res 64:4487-4497. (Pubitemid 38856920)
92. Wesierska-Gadek J, Gueorguieva M, Horky M. 2005a. Roscovitine-induced up-regulation of p53AIP1 protein precedes the onset of apoptosis in human MCF-7 breast cancer cells. Mol Cancer Ther 4:113-124. (Pubitemid 40276781)
93. Wesierska-Gadek J, Gueorguieva M, Ranftler C, Zerza-Schnitzhofer G. 2005b. A new multiplex assay allowing simultaneous detection of the inhibition of cell proliferation and induction of cell death. J Cell Biochem 96:1-7. (Pubitemid 41420095)
94. Wesierska-Gadek J, Schmitz ML, Ranftler C. 2007. Roscovitine-activated HIP2 kinase induces phosphorylation of wt p53 at Ser-46 in human MCF-7 breast cancer cells. J Cell Biochem 100:865-874.
95. Wesierska-Gadek J, Gueorguieva M, Komina O, Schmid G, Kramer MP. 2008. Signaling of DNA damage is not sufficient to induce p53 response; (re)activation of wt p53 protein strongly depends on cellular context. J Cell Biochem 103:1607-1620. (Pubitemid 351490726)
96. Wesierska-Gadek J, Borza A, Walzi E, Krystof V, Maurer M, Komina O, Wandl S. 2009a. Outcome of treatment of human HeLa cervical cancer cells with roscovitine strongly depends on the dosage and cell cycle status prior to the treatment. J Cell Biochem 106:937-955.
97. Wȩsierska-Ga̧dek J, Chamrád I, Kryštof V. 2009b. Novel potent pharmacological cyclin-dependent kinase inhibitors. Future Med Chem 1:1561-1581.
98. Wȩsierska-Ga̧dek J, Gritsch D, Zulehner N, Komina O, Maurer M. 2011a. Roscovitine, a selective CDK inhibitor, reduces the basal and estrogen-induced phosphorylation of ER-α in human ER-positive breast cancer cells. J Cell Biochem (in press) DOI: 10.1002/jcb.23004.
99. Wȩsierska-Ga̧dek J, Hackl S, Zulehner N, Maurer M, Komina O. 2011b. Reconstitution of human MCF-7 breast cancer cells with caspase-3 does not sensitize them to action of CDK inhibitors. J Cell Biochem 112(273):273-288.
100. Wesierska-Gadek J. Maurer M, Zulehner N, Komina O., 2011c Whether to target single or multiple CDKs for therapy? That is the question. J Cell Physiol 226 2 341-349.
101. Wojciechowski J, Horky M, Gueorguieva M, Wesierska-Gadek J. 2003. Rapid onset of nucleolar disintegration preceding cell cycle arrest in roscovitine-induced apoptosis of human MCF-7 breast cancer cells. Int J Cancer 106: 486-495. (Pubitemid 36969788)
102. Zulehner N, Maurer M, Wȩsierska-Ga̧dek J. 2011. Effect of anti-estrogen combined with roscovitine, a selective CDK inhibitor, on human breast cancer cells differing in expression of ER. J Exp Therap Oncol 9:17-25.