Expression of specificity protein transcription factors in pancreatic cancer and their association in prognosis and therapy

Current Medicinal Chemistry

Volumn 19, Issue 22, 2012, Pages 3779-3786

  Sankpal, Umesh T ^a   Maliakal, Pius ^a   Bose, Debashish ^a   Kayaleh, Omar ^a   Buchholz, Daniel ^a   Basha, Riyaz ^a  

^a M D ANDERSON CANCER CENTER ORLANDO   (United States)

Author keywords

Mucins; Pancreatic cancer; Sp1; Survivin; Transcription factors

Indexed keywords

BETULIC ACID; BEVACIZUMAB; CELECOXIB; CURCUMIN; CYTOKERATIN 19; MITHRAMYCIN; MUCIN; NONSTEROID ANTIINFLAMMATORY AGENT; TOLFENAMIC ACID; TRANSCRIPTION FACTOR; TRANSFORMING GROWTH FACTOR BETA; TUMOR MARKER;

ANGIOGENESIS; ANTINEOPLASTIC ACTIVITY; BREAST CANCER; CANCER CELL CULTURE; CANCER INHIBITION; CANCER SURVIVAL; CANCER THERAPY; CELL DIFFERENTIATION; CELL MIGRATION; CELL PROLIFERATION; COLORECTAL CANCER; DRUG POTENTIATION; ENDOPLASMIC RETICULUM STRESS; ESOPHAGUS CANCER; HEADACHE; HUMAN; LEUKEMIA; MESENCHYMAL STEM CELL; METASTASIS; MIGRAINE; MOUTH CANCER; NEUROBLASTOMA; NONHUMAN; OVARY CANCER; PANCREAS CANCER; PROGNOSIS; PROSTATE CANCER; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN FUNCTION; REVIEW; TESTIS CANCER; UPREGULATION; UTERINE CERVIX CANCER;

ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ENDOPLASMIC RETICULUM STRESS; EPITHELIAL-MESENCHYMAL TRANSITION; HUMANS; KERATIN-19; MUCINS; NEOVASCULARIZATION, PATHOLOGIC; PANCREATIC NEOPLASMS; PROGNOSIS; SP TRANSCRIPTION FACTORS; TRANSFORMING GROWTH FACTOR BETA;

EID: 84865210270     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/092986712801661077     Document Type: Review

References (127)

1. Jemal, A.; Siegel, R.; Ward, E.; Hao, Y.; Xu, J.; and Thun, M.J., Cancer statistics, 2009. CA Cancer J Clin, 2009. 59(4), 225-49.
2. American Cancer Society: Cancer Facts and Figures -2012. American Cancer Society, 2012.
3. Wagner, M.; Redaelli, C.; Lietz, M.; Seiler, C.A.; Friess, H.; and Buchler, M.W., Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg, 2004. 91(5), 586-94. (Pubitemid 38624667)
4. Conlon, K.C.; Klimstra, D.S.; and Brennan, M.F., Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg, 1996. 223(3), 273-9. (Pubitemid 26086718)
5. Hidalgo, M., Pancreatic cancer. N Engl J Med, 2010. 362(17), 1605-17.
6. Maitra, A. and Hruban, R.H., Pancreatic cancer. Annu Rev Pathol, 2008. 3, 157-88. (Pubitemid 351488279)
7. Wilentz, R.E.; Geradts, J.; Maynard, R.; Offerhaus, G.J.; Kang, M.; Goggins, M.; Yeo, C.J.; Kern, S.E.; and Hruban, R.H., Inactivation of the p16 (INK4A) tumor-suppressor gene in pancreatic duct lesions: loss of intranuclear expression. Cancer Res, 1998. 58(20), 4740-4. (Pubitemid 28480644)
8. Tascilar, M.; Skinner, H.G.; Rosty, C.; Sohn, T.; Wilentz, R.E.; Offerhaus, G.J.; Adsay, V.; Abrams, R.A.; Cameron, J.L.; Kern, S.E.; Yeo, C.J.; Hruban, R.H.; and Goggins, M., The SMAD4 protein and prognosis of pancreatic ductal adenocarcinoma. Clin Cancer Res, 2001. 7(12), 4115-21. (Pubitemid 34044636)
9. Hruban, R.H.; Iacobuzio-Donahue, C.; Wilentz, R.E.; Goggins, M.; and Kern, S.E., Molecular pathology of pancreatic cancer. Cancer J, 2001. 7(4), 251-8.
10. Yu, J.; Ohuchida, K.; Mizumoto, K.; Ishikawa, N.; Ogura, Y.; Yamada, D.; Egami, T.; Fujita, H.; Ohashi, S.; Nagai, E.; and Tanaka, M., Overexpression of c-met in the early stage of pancreatic carcinogenesis; altered expression is not sufficient for progression from chronic pancreatitis to pancreatic cancer. World J Gastroenterol, 2006. 12(24), 3878-82. (Pubitemid 44028401)
11. Otte, J.M.; Kiehne, K.; Schmitz, F.; Folsch, U.R.; and Herzig, K.H., C-met protooncogene expression and its regulation by cytokines in the regenerating pancreas and in pancreatic cancer cells. Scand J Gastroenterol, 2000. 35(1), 90-5. (Pubitemid 30066778)
12. Thayer, S.P.; di Magliano, M.P.; Heiser, P.W.; Nielsen, C.M.; Roberts, D.J.; Lauwers, G.Y.; Qi, Y.P.; Gysin, S.; Fernandez-del Castillo, C.; Yajnik, V.; Antoniu, B.; McMahon, M.; Warshaw, A.L.; and Hebrok, M., Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature, 2003. 425(6960), 851-6. (Pubitemid 37355945)
13. Ji, Z.; Mei, F.C.; Xie, J.; and Cheng, X., Oncogenic KRAS activates hedgehog signaling pathway in pancreatic cancer cells. J Biol Chem, 2007. 282(19), 14048-55. (Pubitemid 47100411)
14. Miyamoto, Y.; Maitra, A.; Ghosh, B.; Zechner, U.; Argani, P.; Iacobuzio-Donahue, C.A.; Sriuranpong, V.; Iso, T.; Meszoely, I.M.; Wolfe, M.S.; Hruban, R.H.; Ball, D.W.; Schmid, R.M.; and Leach, S.D., Notch mediates TGF alpha-induced changes in epithelial differentiation during pancreatic tumorigenesis. Cancer Cell, 2003. 3(6), 565-76. (Pubitemid 36808651)
15. Terris, B.; Blaveri, E.; Crnogorac-Jurcevic, T.; Jones, M.; Missiaglia, E.; Ruszniewski, P.; Sauvanet, A.; and Lemoine, N.R., Characterization of gene expression profiles in intraductal papillary-mucinous tumors of the pancreas. Am J Pathol, 2002. 160(5), 1745-54. (Pubitemid 34525654)
16. Fukushima, N.; Sato, N.; Prasad, N.; Leach, S.D.; Hruban, R.H.; and Goggins, M., Characterization of gene expression in mucinous cystic neoplasms of the pancreas using oligonucleotide microarrays. Oncogene, 2004. 23(56), 9042-51. (Pubitemid 40013071)
17. Wang, Z.; Ahmad, A.; Li, Y.; Azmi, A.S.; Miele, L.; and Sarkar, F.H., Targeting notch to eradicate pancreatic cancer stem cells for cancer therapy. Anticancer Res, 2011. 31(4), 1105-13.
18. Roy, S.K.; Srivastava, R.K.; and Shankar, S., Inhibition of PI3K/AKT and MAPK/ERK pathways causes activation of FOXO transcription factor, leading to cell cycle arrest and apoptosis in pancreatic cancer. J Mol Signal, 2010. 5, 10.
19. Yao, Z.; Okabayashi, Y.; Yutsudo, Y.; Kitamura, T.; Ogawa, W.; and Kasuga, M., Role of Akt in growth and survival of PANC-1 pancreatic cancer cells. Pancreas, 2002. 24(1), 42-6. (Pubitemid 34019658)
20. Ma, J.; Sawai, H.; Ochi, N.; Matsuo, Y.; Xu, D.; Yasuda, A.; Takahashi, H.; Wakasugi, T.; and Takeyama, H., PTEN regulates angiogenesis through PI3K/Akt/VEGF signaling pathway in human pancreatic cancer cells. Mol Cell Biochem, 2009. 331(1-2), 161-71.
21. Ripka, S.; Neesse, A.; Riedel, J.; Bug, E.; Aigner, A.; Poulsom, R.; Fulda, S.; Neoptolemos, J.; Greenhalf, W.; Barth, P.; Gress, T.M.; and Michl, P., CUX1: target of Akt signalling and mediator of resistance to apoptosis in pancreatic cancer. Gut, 2010. 59(8), 1101-10.
22. Sahu, R.P. and Srivastava, S.K., The role of STAT-3 in the induction of apoptosis in pancreatic cancer cells by benzyl isothiocyanate. J Natl Cancer Inst, 2009. 101(3), 176-93.
23. Rulifson, I.C.; Karnik, S.K.; Heiser, P.W.; ten Berge, D.; Chen, H.; Gu, X.; Taketo, M.M.; Nusse, R.; Hebrok, M.; and Kim, S.K., Wnt signaling regulates pancreatic beta cell proliferation. Proc Natl Acad Sci U S A, 2007. 104(15), 6247-52. (Pubitemid 47186080)
24. Al-Aynati, M.M.; Radulovich, N.; Riddell, R.H.; and Tsao, M.S., Epithelialcadherin and beta-catenin expression changes in pancreatic intraepithelial neoplasia. Clin Cancer Res, 2004. 10(4), 1235-40. (Pubitemid 38365212)
25. Kadonaga, J.T.; Carner, K.R.; Masiarz, F.R.; and Tjian, R., Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain. Cell, 1987. 51(6), 1079-90.
26. Kadonaga, J.T.; Courey, A.J.; Ladika, J.; and Tjian, R., Distinct regions of Sp1 modulate DNA binding and transcriptional activation. Science, 1988. 242(4885), 1566-70.
27. Suske, G.; Bruford, E.; and Philipsen, S., Mammalian SP/KLF transcription factors: bring in the family. Genomics, 2005. 85(5), 551-6. (Pubitemid 40463690)
28. Sankpal, U.T.; Goodison, S.; Abdelrahim, M.; and Basha, R., Targeting Sp1 transcription factors in prostate cancer therapy. Med Chem, 2011. 7(5), 518-25.
29. Suske, G., The Sp-family of transcription factors. Gene, 1999. 238(2), 291-300. (Pubitemid 29446168)
30. Hagen, G.; Muller, S.; Beato, M.; and Suske, G., Cloning by recognition site screening of two novel GT box binding proteins: a family of Sp1 related genes. Nucleic Acids Res, 1992. 20(21), 5519-25.
31. Waby, J.S.; Bingle, C.D.; and Corfe, B.M., Post-translational control of spfamily transcription factors. Curr Genomics, 2008. 9(5), 301-11.
32. Bouwman, P. and Philipsen, S., Regulation of the activity of Sp1-related transcription factors. Mol Cell Endocrinol, 2002. 195(1-2), 27-38. (Pubitemid 35287159)
33. Cawley, S.; Bekiranov, S.; Ng, H.H.; Kapranov, P.; Sekinger, E.A.; Kampa, D.; Piccolboni, A.; Sementchenko, V.; Cheng, J.; Williams, A.J.; Wheeler, R.; Wong, B.; Drenkow, J.; Yamanaka, M.; Patel, S.; Brubaker, S.; Tammana, H.; Helt, G.; Struhl, K.; and Gingeras, T.R., Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell, 2004. 116(4), 499-509. (Pubitemid 38264428)
34. Marin, M.; Karis, A.; Visser, P.; Grosveld, F.; and Philipsen, S., Transcription factor Sp1 is essential for early embryonic development but dispensable for cell growth and differentiation. Cell, 1997. 89(4), 619-28. (Pubitemid 27511772)
35. Bouwman, P.; Gollner, H.; Elsasser, H.P.; Eckhoff, G.; Karis, A.; Grosveld, F.; Philipsen, S.; and Suske, G., Transcription factor Sp3 is essential for postnatal survival and late tooth development. EMBO J, 2000. 19(4), 655-61. (Pubitemid 30093738)
36. Wierstra, I., Sp1: emerging roles-beyond constitutive activation of TATAless housekeeping genes. Biochem Biophys Res Commun, 2008. 372(1), 1-13.
37. Tapias, A.; Ciudad, C.J.; Roninson, I.B.; and Noe, V., Regulation of Sp1 by cell cycle related proteins. Cell Cycle, 2008. 7(18), 2856-67.
38. Deniaud, E.; Baguet, J.; Mathieu, A.L.; Pages, G.; Marvel, J.; and Leverrier, Y., Overexpression of Sp1 transcription factor induces apoptosis. Oncogene, 2006. 25(53), 7096-105. (Pubitemid 44722077)
39. Kaczynski, J.; Cook, T.; and Urrutia, R., Sp1-and Kruppel-like transcription factors. Genome Biol, 2003. 4(2), 206.
40. Safe, S. and Abdelrahim, M., Sp transcription factor family and its role in cancer. Eur J Cancer, 2005. 41(16), 2438-48. (Pubitemid 41540621)
41. Shi, Q.; Le, X.; Abbruzzese, J.L.; Peng, Z.; Qian, C.N.; Tang, H.; Xiong, Q.; Wang, B.; Li, X.C.; and Xie, K., Constitutive Sp1 activity is essential for differential constitutive expression of vascular endothelial growth factor in human pancreatic adenocarcinoma. Cancer Res, 2001. 61(10), 4143-54. (Pubitemid 32720983)
42. Yao, J.C.; Wang, L.; Wei, D.; Gong, W.; Hassan, M.; Wu, T.T.; Mansfield, P.; Ajani, J.; and Xie, K., Association between expression of transcription factor Sp1 and increased vascular endothelial growth factor expression, advanced stage, and poor survival in patients with resected gastric cancer. Clin Cancer Res, 2004. 10(12 Pt 1), 4109-17. (Pubitemid 38812490)
43. Zannetti, A.; Del Vecchio, S.; Carriero, M.V.; Fonti, R.; Franco, P.; Botti, G.; D'Aiuto, G.; Stoppelli, M.P.; and Salvatore, M., Coordinate up-regulation of Sp1 DNA-binding activity and urokinase receptor expression in breast carcinoma. Cancer Res, 2000. 60(6), 1546-51. (Pubitemid 30183423)
44. Chiefari, E.; Brunetti, A.; Arturi, F.; Bidart, J.M.; Russo, D.; Schlumberger, M.; and Filetti, S., Increased expression of AP2 and Sp1 transcription factors in human thyroid tumors: a role in NIS expression regulation? BMC Cancer, 2002. 2, 35.
45. Lou, Z.; O'Reilly, S.; Liang, H.; Maher, V.M.; Sleight, S.D.; and McCormick, J.J., Down-regulation of overexpressed sp1 protein in human fibrosarcoma cell lines inhibits tumor formation. Cancer Res, 2005. 65(3), 1007-17. (Pubitemid 40216463)
46. Jungert, K.; Buck, A.; von Wichert, G.; Adler, G.; Konig, A.; Buchholz, M.; Gress, T.M.; and Ellenrieder, V., Sp1 is required for transforming growth factor-beta-induced mesenchymal transition and migration in pancreatic cancer cells. Cancer Res, 2007. 67(4), 1563-70. (Pubitemid 46383380)
47. Blasco, F.; Penuelas, S.; Cascallo, M.; Hernandez, J.L.; Alemany, C.; Masa, M.; Calbo, J.; Soler, M.; Nicolas, M.; Perez-Torras, S.; Gomez, A.; Tarrason, G.; Noe, V.; Mazo, A.; Ciudad, C.J.; and Piulats, J., Expression profiles of a human pancreatic cancer cell line upon induction of apoptosis search for modulators in cancer therapy. Oncology, 2004. 67(3-4), 277-90. (Pubitemid 39551713)
48. Jiang, N.Y.; Woda, B.A.; Banner, B.F.; Whalen, G.F.; Dresser, K.A.; and Lu, D., Sp1, a new biomarker that identifies a subset of aggressive pancreatic ductal adenocarcinoma. Cancer Epidemiol Biomarkers Prev, 2008. 17(7), 1648-52.
49. Wang, L.; Wei, D.; Huang, S.; Peng, Z.; Le, X.; Wu, T.T.; Yao, J.; Ajani, J.; and Xie, K., Transcription factor Sp1 expression is a significant predictor of survival in human gastric cancer. Clin Cancer Res, 2003. 9(17), 6371-80. (Pubitemid 38031822)
50. Itakura, J.; Ishiwata, T.; Friess, H.; Fujii, H.; Matsumoto, Y.; Buchler, M.W.; and Korc, M., Enhanced expression of vascular endothelial growth factor in human pancreatic cancer correlates with local disease progression. Clin Cancer Res, 1997. 3(8), 1309-16. (Pubitemid 27362391)
51. Wang, L.; Guan, X.; Gong, W.; Yao, J.; Peng, Z.; Wei, D.; Wu, T.T.; Huang, S.; and Xie, K., Altered expression of transcription factor Sp1 critically impacts the angiogenic phenotype of human gastric cancer. Clin Exp Metastasis, 2005. 22(3), 205-13. (Pubitemid 41298002)
52. Jungert, K.; Buck, A.; Buchholz, M.; Wagner, M.; Adler, G.; Gress, T.M.; and Ellenrieder, V., Smad-Sp1 complexes mediate TGFbeta-induced early transcription of oncogenic Smad7 in pancreatic cancer cells. Carcinogenesis, 2006. 27(12), 2392-401. (Pubitemid 44884096)
53. Ellenrieder, V.; Hendler, S.F.; Boeck, W.; Seufferlein, T.; Menke, A.; Ruhland, C.; Adler, G.; and Gress, T.M., Transforming growth factor beta1 treatment leads to an epithelial-mesenchymal transdifferentiation of pancreatic cancer cells requiring extracellular signal-regulated kinase 2 activation. Cancer Res, 2001. 61(10), 4222-8. (Pubitemid 32720992)
54. ten Dijke, P. and Hill, C.S., New insights into TGF-beta-Smad signalling. Trends Biochem Sci, 2004. 29(5), 265-73.
55. Datta, P.K.; Blake, M.C.; and Moses, H.L., Regulation of plasminogen activator inhibitor-1 expression by transforming growth factor-beta -induced physical and functional interactions between smads and Sp1. J Biol Chem, 2000. 275(51), 40014-9. (Pubitemid 32064624)
56. Ishibashi, H.; Nakagawa, K.; Onimaru, M.; Castellanous, E.J.; Kaneda, Y.; Nakashima, Y.; Shirasuna, K.; and Sueishi, K., Sp1 decoy transfected to carcinoma cells suppresses the expression of vascular endothelial growth factor, transforming growth factor beta1, and tissue factor and also cell growth and invasion activities. Cancer Res, 2000. 60(22), 6531-6.
57. Ellenrieder, V., TGFbeta regulated gene expression by Smads and Sp1/KLFlike transcription factors in cancer. Anticancer Res, 2008. 28(3A), 1531-9. (Pubitemid 351892926)
58. Harada, H.; Nakagawa, K.; Iwata, S.; Saito, M.; Kumon, Y.; Sakaki, S.; Sato, K.; and Hamada, K., Restoration of wild-type p16 down-regulates vascular endothelial growth factor expression and inhibits angiogenesis in human gliomas. Cancer Res, 1999. 59(15), 3783-9. (Pubitemid 29381887)
59. Kawai, H.; Li, H.; Chun, P.; Avraham, S.; and Avraham, H.K., Direct interaction between BRCA1 and the estrogen receptor regulates vascular endothelial growth factor (VEGF) transcription and secretion in breast cancer cells. Oncogene, 2002. 21(50), 7730-9. (Pubitemid 35398818)
60. Ikeda, N.; Nakajima, Y.; Sho, M.; Adachi, M.; Huang, C.L.; Iki, K.; Kanehiro, H.; Hisanaga, M.; Nakano, H.; and Miyake, M., The association of K-ras gene mutation and vascular endothelial growth factor gene expression in pancreatic carcinoma. Cancer, 2001. 92(3), 488-99. (Pubitemid 32735183)
61. Summy, J.M.; Trevino, J.G.; Baker, C.H.; and Gallick, G.E., c-Src regulates constitutive and EGF-mediated VEGF expression in pancreatic tumor cells through activation of phosphatidyl inositol-3 kinase and p38 MAPK. Pancreas, 2005. 31(3), 263-74. (Pubitemid 41400485)
62. Mayerhofer, M.; Valent, P.; Sperr, W.R.; Griffin, J.D.; and Sillaber, C., BCR/ABL induces expression of vascular endothelial growth factor and its transcriptional activator, hypoxia inducible factor-1alpha, through a pathway involving phosphoinositide 3-kinase and the mammalian target of rapamycin. Blood, 2002. 100(10), 3767-75. (Pubitemid 35303950)
63. Xie, K.; Wei, D.; and Huang, S., Transcriptional anti-angiogenesis therapy of human pancreatic cancer. Cytokine Growth Factor Rev, 2006. 17(3), 147-56. (Pubitemid 43816895)
64. Wei, D.; Le, X.; Zheng, L.; Wang, L.; Frey, J.A.; Gao, A.C.; Peng, Z.; Huang, S.; Xiong, H.Q.; Abbruzzese, J.L.; and Xie, K., Stat3 activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis. Oncogene, 2003. 22(3), 319-29. (Pubitemid 36194328)
65. Schwarte-Waldhoff, I.; Volpert, O.V.; Bouck, N.P.; Sipos, B.; Hahn, S.A.; Klein-Scory, S.; Luttges, J.; Kloppel, G.; Graeven, U.; Eilert-Micus, C.; Hintelmann, A.; and Schmiegel, W., Smad4/DPC4-mediated tumor suppression through suppression of angiogenesis. Proc Natl Acad Sci U S A, 2000. 97(17), 9624-9. (Pubitemid 30650826)
66. Fujioka, S.; Niu, J.; Schmidt, C.; Sclabas, G.M.; Peng, B.; Uwagawa, T.; Li, Z.; Evans, D.B.; Abbruzzese, J.L.; and Chiao, P.J., NF-kappaB and AP-1 connection: mechanism of NF-kappaB-dependent regulation of AP-1 activity. Mol Cell Biol, 2004. 24(17), 7806-19. (Pubitemid 39121503)
67. Buchler, P.; Reber, H.A.; Buchler, M.; Shrinkante, S.; Buchler, M.W.; Friess, H.; Semenza, G.L.; and Hines, O.J., Hypoxia-inducible factor 1 regulates vascular endothelial growth factor expression in human pancreatic cancer. Pancreas, 2003. 26(1), 56-64. (Pubitemid 36020267)
68. Abdelrahim, M.; Smith, R., 3rd; Burghardt, R.; and Safe, S., Role of Sp proteins in regulation of vascular endothelial growth factor expression and proliferation of pancreatic cancer cells. Cancer Res, 2004. 64(18), 6740-9. (Pubitemid 39297937)
69. Abdelrahim, M.; Baker, C.H.; Abbruzzese, J.L.; Sheikh-Hamad, D.; Liu, S.; Cho, S.D.; Yoon, K.; and Safe, S., Regulation of vascular endothelial growth factor receptor-1 expression by specificity proteins 1, 3, and 4 in pancreatic cancer cells. Cancer Res, 2007. 67(7), 3286-94. (Pubitemid 46724867)
70. Higgins, K.J.; Abdelrahim, M.; Liu, S.; Yoon, K.; and Safe, S., Regulation of vascular endothelial growth factor receptor-2 expression in pancreatic cancer cells by Sp proteins. Biochem Biophys Res Commun, 2006. 345(1), 292-301. (Pubitemid 44269283)
71. Ho, S.B.; Shekels, L.L.; Toribara, N.W.; Kim, Y.S.; Lyftogt, C.; Cherwitz, D.L.; and Niehans, G.A., Mucin gene expression in normal, preneoplastic, and neoplastic human gastric epithelium. Cancer Res, 1995. 55(12), 2681-90.
72. Kim, G.E.; Bae, H.I.; Park, H.U.; Kuan, S.F.; Crawley, S.C.; Ho, J.J.; and Kim, Y.S., Aberrant expression of MUC5AC and MUC6 gastric mucins and sialyl Tn antigen in intraepithelial neoplasms of the pancreas. Gastroenterology, 2002. 123(4), 1052-60.
73. Kato, S.; Hokari, R.; Crawley, S.; Gum, J.; Ahn, D.H.; Kim, J.W.; Kwon, S.W.; Miura, S.; Basbaum, C.B.; and Kim, Y.S., MUC5AC mucin gene regulation in pancreatic cancer cells. Int J Oncol, 2006. 29(1), 33-40.
74. Perrais, M.; Pigny, P.; Ducourouble, M.P.; Petitprez, D.; Porchet, N.; Aubert, J.P.; and Van Seuningen, I., Characterization of human mucin gene MUC4 promoter: importance of growth factors and proinflammatory cytokines for its regulation in pancreatic cancer cells. J Biol Chem, 2001. 276(33), 30923-33.
75. Vincent, A.; Ducourouble, M.P.; and Van Seuningen, I., Epigenetic regulation of the human mucin gene MUC4 in epithelial cancer cell lines involves both DNA methylation and histone modifications mediated by DNA methyltransferases and histone deacetylases. FASEB J, 2008. 22(8), 3035-45.
76. Adsay, N.V.; Merati, K.; Andea, A.; Sarkar, F.; Hruban, R.H.; Wilentz, R.E.; Goggins, M.; Iocobuzio-Donahue, C.; Longnecker, D.S.; and Klimstra, D.S., The dichotomy in the preinvasive neoplasia to invasive carcinoma sequence in the pancreas: differential expression of MUC1 and MUC2 supports the existence of two separate pathways of carcinogenesis. Mod Pathol, 2002. 15(10), 1087-95.
77. Pantano, F.; Baldi, A.; Santini, D.; Vincenzi, B.; Borzomati, D.; Vecchio, F.M.; Castri, F.; Antinori, A.; Caraglia, M.; Magistrelli, P.; Coppola, R.; and Tonini, G., MUC2 but not MUC5 expression correlates with prognosis in radically resected pancreatic cancer patients. Cancer Biol Ther, 2009. 8(11), 996-9.
78. Velcich, A.; Yang, W.; Heyer, J.; Fragale, A.; Nicholas, C.; Viani, S.; Kucherlapati, R.; Lipkin, M.; Yang, K.; and Augenlicht, L., Colorectal cancer in mice genetically deficient in the mucin Muc2. Science, 2002. 295(5560), 1726-9. (Pubitemid 34202910)
79. Gum, J.R.; Hicks, J.W.; and Kim, Y.S., Identification and characterization of the MUC2 (human intestinal mucin) gene 5'-flanking region: promoter activity in cultured cells. Biochem J, 1997. 325 (Pt 1), 259-67.
80. Velcich, A.; Palumbo, L.; Selleri, L.; Evans, G.; and Augenlicht, L., Organization and regulatory aspects of the human intestinal mucin gene (MUC2) locus. J Biol Chem, 1997. 272(12), 7968-76. (Pubitemid 27137360)
81. Perrais, M.; Pigny, P.; Copin, M.C.; Aubert, J.P.; and Van Seuningen, I., Induction of MUC2 and MUC5AC mucins by factors of the epidermal growth factor (EGF) family is mediated by EGF receptor/Ras/Raf/extracellular signal-regulated kinase cascade and Sp1. J Biol Chem, 2002. 277(35), 32258-67. (Pubitemid 34969042)
82. Ho, J.J.; Han, S.W.; Pan, P.L.; Deng, G.; Kuan, S.F.; and Kim, Y.S., Methylation status of promoters and expression of MUC2 and MUC5AC mucins in pancreatic cancer cells. Int J Oncol, 2003. 22(2), 273-9.
83. Hamada, T.; Goto, M.; Tsutsumida, H.; Nomoto, M.; Higashi, M.; Sugai, T.; Nakamura, S.; and Yonezawa, S., Mapping of the methylation pattern of the MUC2 promoter in pancreatic cancer cell lines, using bisulfite genomic sequencing. Cancer Lett, 2005. 227(2), 175-84. (Pubitemid 41169931)
84. Abdelrahim, M.; Liu, S.; and Safe, S., Induction of endoplasmic reticuluminduced stress genes in Panc-1 pancreatic cancer cells is dependent on Sp proteins. J Biol Chem, 2005. 280(16), 16508-13. (Pubitemid 40616782)
85. Racek, T.; Buhlmann, S.; Rust, F.; Knoll, S.; Alla, V.; and Putzer, B.M., Transcriptional repression of the prosurvival endoplasmic reticulum chaperone GRP78/BIP by E2F1. J Biol Chem, 2008. 283(49), 34305-14.
86. La Rosa, S.; Rigoli, E.; Uccella, S.; Novario, R.; and Capella, C., Prognostic and biological significance of cytokeratin 19 in pancreatic endocrine tumours. Histopathology, 2007. 50(5), 597-606. (Pubitemid 46495832)
87. Brembeck, F.H. and Rustgi, A.K., The tissue-dependent keratin 19 gene transcription is regulated by GKLF/KLF4 and Sp1. J Biol Chem, 2000. 275(36), 28230-9.
88. Ray, R.; Snyder, R.C.; Thomas, S.; Koller, C.A.; and Miller, D.M., Mithramycin blocks protein binding and function of the SV40 early promoter. J Clin Invest, 1989. 83(6), 2003-7. (Pubitemid 19148872)
89. Blume, S.W.; Snyder, R.C.; Ray, R.; Thomas, S.; Koller, C.A.; and Miller, D.M., Mithramycin inhibits SP1 binding and selectively inhibits transcriptional activity of the dihydrofolate reductase gene in vitro and in vivo. J Clin Invest, 1991. 88(5), 1613-21.
90. Torrance, C.J.; Agrawal, V.; Vogelstein, B.; and Kinzler, K.W., Use of isogenic human cancer cells for high-throughput screening and drug discovery. Nat Biotechnol, 2001. 19(10), 940-5. (Pubitemid 32947572)
91. Yuan, P.; Wang, L.; Wei, D.; Zhang, J.; Jia, Z.; Li, Q.; Le, X.; Wang, H.; Yao, J.; and Xie, K., Therapeutic inhibition of Sp1 expression in growing tumors by mithramycin a correlates directly with potent antiangiogenic effects on human pancreatic cancer. Cancer, 2007. 110(12), 2682-90. (Pubitemid 350250337)
92. Jia, Z.; Zhang, J.; Wei, D.; Wang, L.; Yuan, P.; Le, X.; Li, Q.; Yao, J.; and Xie, K., Molecular basis of the synergistic antiangiogenic activity of bevacizumab and mithramycin A. Cancer Res, 2007. 67(10), 4878-85. (Pubitemid 46910196)
93. Jia, Z.; Gao, Y.; Wang, L.; Li, Q.; Zhang, J.; Le, X.; Wei, D.; Yao, J.C.; Chang, D.Z.; Huang, S.; and Xie, K., Combined treatment of pancreatic cancer with mithramycin A and tolfenamic acid promotes Sp1 degradation and synergistic antitumor activity. Cancer research, 2010. 70(3), 1111-9.
94. Gao, Y.; Jia, Z.; Kong, X.; Li, Q.; Chang, D.Z.; Wei, D.; Le, X.; Suyun, H.; Huang, S.; Wang, L.; and Xie, K., Combining betulinic acid and mithramycin a effectively suppresses pancreatic cancer by inhibiting proliferation, invasion, and angiogenesis. Cancer Res, 2011. 71(15), 5182-93.
95. Wei, D.; Wang, L.; He, Y.; Xiong, H.Q.; Abbruzzese, J.L.; and Xie, K., Celecoxib inhibits vascular endothelial growth factor expression in and reduces angiogenesis and metastasis of human pancreatic cancer via suppression of Sp1 transcription factor activity. Cancer Res, 2004. 64(6), 2030-8. (Pubitemid 38339450)
96. Abdelrahim, M.; Baker, C.H.; Abbruzzese, J.L.; and Safe, S., Tolfenamic acid and pancreatic cancer growth, angiogenesis, and Sp protein degradation. J Natl Cancer Inst, 2006. 98(12), 855-68. (Pubitemid 43923442)
97. Basha, R.; Ingersoll, S.B.; Sankpal, U.T.; Ahmad, S.; Baker, C.H.; Edwards, J.R.; Holloway, R.W.; Kaja, S.; and Abdelrahim, M., Tolfenamic acid inhibits ovarian cancer cell growth and decreases the expression of c-Met and survivin through suppressing specificity protein transcription factors. Gynecol Oncol, 2011. 122(1), 163-70.
98. Colon, J.; Basha, M.R.; Madero-Visbal, R.; Konduri, S.; Baker, C.H.; Herrera, L.J.; Safe, S.; Sheikh-Hamad, D.; Abudayyeh, A.; Alvarado, B.; and Abdelrahim, M., Tolfenamic acid decreases c-Met expression through Sp proteins degradation and inhibits lung cancer cells growth and tumor formation in orthotopic mice. Invest New Drugs, 2011. 29(1), 41-51.
99. Altenburger, D.L.; Wagner, A.S.; Eslin, D.E.; Pearl, G.S.; and Pattisapu, J.V., A rare case of malignant pediatric ectomesenchymoma arising from the falx cerebri. J Neurosurg Pediatr, 2011. 7(1), 94-7.
100. Kim, J.H.; Jung, J.Y.; Shim, J.H.; Kim, J.; Choi, K.H.; Shin, J.A.; Choi, E.S.; Lee, S.O.; Chintharlapalli, S.; Kwon, K.H.; Leem, D.H.; Cho, N.P.; and Cho, S.D., Apoptotic Effect of Tolfenamic Acid in KB Human Oral Cancer Cells: Possible Involvement of the p38 MAPK Pathway. J Clin Biochem Nutr, 2010. 47(1), 74-80.
101. Lee, S.H.; Bahn, J.H.; Choi, C.K.; Whitlock, N.C.; English, A.E.; Safe, S.; and Baek, S.J., ESE-1/EGR-1 pathway plays a role in tolfenamic acidinduced apoptosis in colorectal cancer cells. Mol Cancer Ther, 2008. 7(12), 3739-50.
102. Liu, X.; Abdelrahim, M.; Abudayyeh, A.; Lei, P.; and Safe, S., The nonsteroidal anti-inflammatory drug tolfenamic acid inhibits BT474 and SKBR3 breast cancer cell and tumor growth by repressing erbB2 expression. Mol Cancer Ther, 2009. 8(5), 1207-17.
103. Maliakal, P.; Abdelrahim, M.; Sankpal, U.T.; Maliakal, C.; Baker, C.H.; Safe, S.; Herrera, L.J.; Abudayyeh, A.; Kaja, S.; and Basha, R., Chemopreventive effects of tolfenamic acid against esophageal tumorigenesis in rats. Invest New Drugs, 2011.
104. Papineni, S.; Chintharlapalli, S.; Abdelrahim, M.; Lee, S.O.; Burghardt, R.; Abudayyeh, A.; Baker, C.; Herrera, L.; and Safe, S., Tolfenamic acid inhibits esophageal cancer through repression of specificity proteins and c-Met. Carcinogenesis, 2009. 30(7), 1193-201.
105. Shim, J.H.; Shin, J.A.; Jung, J.Y.; Choi, K.H.; Choi, E.S.; Cho, N.P.; Kong, G.; Ryu, M.H.; Chae, J.I.; and Cho, S.D., Chemopreventive effect of tolfenamic acid on KB human cervical cancer cells and tumor xenograft by downregulating specificity protein 1. Eur J Cancer Prev, 2011. 20(2), 102-11.
106. Li, L.; Aggarwal, B.B.; Shishodia, S.; Abbruzzese, J.; and Kurzrock, R., Nuclear factor-kappaB and IkappaB kinase are constitutively active in human pancreatic cells, and their down-regulation by curcumin (diferuloylmethane) is associated with the suppression of proliferation and the induction of apoptosis. Cancer, 2004. 101(10), 2351-62. (Pubitemid 39458693)
107. Jutooru, I.; Chadalapaka, G.; Lei, P.; and Safe, S., Inhibition of NFkappaB and pancreatic cancer cell and tumor growth by curcumin is dependent on specificity protein down-regulation. The Journal of biological chemistry, 2010. 285(33), 25332-44.
108. Kami, K.; Doi, R.; Koizumi, M.; Toyoda, E.; Mori, T.; Ito, D.; Fujimoto, K.; Wada, M.; Miyatake, S.; and Imamura, M., Survivin expression is a prognostic marker in pancreatic cancer patients. Surgery, 2004. 136(2), 443-8. (Pubitemid 39037686)
109. Kami, K.; Doi, R.; Koizumi, M.; Toyoda, E.; Mori, T.; Ito, D.; Kawaguchi, Y.; Fujimoto, K.; Wada, M.; Miyatake, S.; and Imamura, M., Downregulation of survivin by siRNA diminishes radioresistance of pancreatic cancer cells. Surgery, 2005. 138(2), 299-305. (Pubitemid 41253814)
110. Konduri, S.; Colon, J.; Baker, C.H.; Safe, S.; Abbruzzese, J.L.; Abudayyeh, A.; Basha, M.R.; and Abdelrahim, M., Tolfenamic acid enhances pancreatic cancer cell and tumor response to radiation therapy by inhibiting survivin protein expression. Mol Cancer Ther, 2009. 8(3), 533-42.
111. Li, F. and Altieri, D.C., Transcriptional analysis of human survivin gene expression. Biochem J, 1999. 344 Pt 2, 305-11. (Pubitemid 30011584)
112. Lee, S.O.; Chintharlapalli, S.; Liu, S.; Papineni, S.; Cho, S.D.; Yoon, K.; and Safe, S., p21 expression is induced by activation of nuclear nerve growth factor-induced Balpha (Nur77) in pancreatic cancer cells. Mol Cancer Res, 2009. 7(7), 1169-78.
113. Hong, J.; Samudio, I.; Liu, S.; Abdelrahim, M.; and Safe, S., Peroxisome proliferator-activated receptor gamma-dependent activation of p21 in Panc-28 pancreatic cancer cells involves Sp1 and Sp4 proteins. Endocrinology, 2004. 145(12), 5774-85. (Pubitemid 39564619)
114. Hamada, S.; Satoh, K.; Hirota, M.; Kanno, A.; Umino, J.; Ito, H.; Masamune, A.; Kikuta, K.; Kume, K.; and Shimosegawa, T., The homeobox gene MSX2 determines chemosensitivity of pancreatic cancer cells via the regulation of transporter gene ABCG2. J Cell Physiol, 2012. 227(2), 729-38.
115. Bailey-Dell, K.J.; Hassel, B.; Doyle, L.A.; and Ross, D.D., Promoter characterization and genomic organization of the human breast cancer resistance protein (ATP-binding cassette transporter G2) gene. Biochim Biophys Acta, 2001. 1520(3), 234-41. (Pubitemid 32868794)
116. Pickles, M. and Leask, A., Analysis of CCN2 promoter activity in PANC-1 cells: regulation by ras/MEK/ERK. J Cell Commun Signal, 2007. 1(2), 85-90.
117. Kwon, S.; Munroe, X.; Crawley, S.C.; Lee, H.Y.; Spong, S.; Bradham, D.; Gum, J.R., Jr.; Sleisenger, M.H.; and Kim, Y.S., Expression of connective tissue growth factor in pancreatic cancer cell lines. Int J Oncol, 2007. 31(4), 693-703.
118. Kominato, Y.; Iida, R.; Nakajima, T.; Tajima, Y.; Takagi, R.; Makita, C.; Kishi, K.; Ueki, M.; Kawai, Y.; and Yasuda, T., Hypoxia induces upregulation of the deoxyribonuclease I gene in the human pancreatic cancer cell line QGP-1. Biochim Biophys Acta, 2007. 1770(11), 1567-75. (Pubitemid 47503561)
119. Kominato, Y.; Ueki, M.; Iida, R.; Kawai, Y.; Nakajima, T.; Makita, C.; Itoi, M.; Tajima, Y.; Kishi, K.; and Yasuda, T., Characterization of human deoxyribonuclease I gene (DNASE1) promoters reveals the utilization of two transcription-starting exons and the involvement of Sp1 in its transcriptional regulation. FEBS J, 2006. 273(13), 3094-105.
120. Zboralski, D.; Bockmann, M.; Zapatka, M.; Hoppe, S.; Schoneck, A.; Hahn, S.A.; Schmiegel, W.; and Schwarte-Waldhoff, I., Divergent mechanisms underlie Smad4-mediated positive regulation of the three genes encoding the basement membrane component laminin-332 (laminin-5). BMC Cancer, 2008. 8, 215.
121. Asomaning, K.; Reid, A.E.; Zhou, W.; Heist, R.S.; Zhai, R.; Su, L.; Kwak, E.L.; Blaszkowsky, L.; Zhu, A.X.; Ryan, D.P.; Christiani, D.C.; and Liu, G., MDM2 promoter polymorphism and pancreatic cancer risk and prognosis. Clin Cancer Res, 2008. 14(12), 4010-5.
122. Knappskog, S. and Lonning, P.E., MDM2 promoter SNP285 and SNP309; phylogeny and impact on cancer risk. Oncotarget, 2011. 2(3), 251-8.
123. Barrasa, J.I.; Olmo, N.; Santiago-Gomez, A.; Lecona, E.; Anglard, P.; Turnay, J.; and Lizarbe, M.A., Histone deacetylase inhibitors upregulate MMP11 gene expression through Sp1/Smad complexes in human colon adenocarcinoma cells. Biochim Biophys Acta, 2012. 1823(2), 570-81.
124. Singh, A.P.; Chaturvedi, P.; and Batra, S.K., Emerging roles of MUC4 in cancer: a novel target for diagnosis and therapy. Cancer Res, 2007. 67(2), 433-6. (Pubitemid 46192176)
125. Jutooru, I.; Chadalapaka, G.; Abdelrahim, M.; Basha, M.R.; Samudio, I.; Konopleva, M.; Andreeff, M.; and Safe, S., Methyl 2-cyano-3, 12-dioxooleana-1, 9-dien-28-oate decreases specificity protein transcription factors and inhibits pancreatic tumor growth: role of microRNA-27a. Molecular pharmacology, 2010. 78(2), 226-36.
126. Huang, W.; Zhao, S.; Ammanamanchi, S.; Brattain, M.; Venkatasubbarao, K.; and Freeman, J.W., Trichostatin A induces transforming growth factor beta type II receptor promoter activity and acetylation of Sp1 by recruitment of PCAF/p300 to a Sp1.NF-Y complex. J Biol Chem, 2005. 280(11), 10047-54. (Pubitemid 40395856)
127. Zhao, S.; Venkatasubbarao, K.; Li, S.; and Freeman, J.W., Requirement of a specific Sp1 site for histone deacetylase-mediated repression of transforming growth factor beta Type II receptor expression in human pancreatic cancer cells. Cancer Res, 2003, 63(10), 2624-30. (Pubitemid 36605205)