A review on hepatocyte nuclear factor-1beta and tumor

Springer Science and Business Media LLC - Tập 5 - Trang 1-8 - 2015
Dan-Dan Yu1, Shi-Wei Guo1, Ying-Ying Jing1, Yu-Long Dong1, Li-Xin Wei1
1Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China

Tóm tắt

Hepatocyte nuclear factor-1beta (HNF1β) was initially identified as a liver-specific transcription factor. It is a homeobox transcription factor that functions as a homodimer or heterodimer with HNF1α. HNF1β plays an important role in organogenesis during embryonic stage, especially of the liver, kidney, and pancreas. Mutations in the HNF1β gene cause maturity-onset diabetes of the young type 5 (MODY5), renal cysts, genital malformations, and pancreas atrophy. Recently, it has been shown that the expression of HNF1β is associated with cancer risk in several tumors, including hepatocellular carcinoma, pancreatic carcinoma, renal cancer, ovarian cancer, endometrial cancer, and prostate cancer. HNF1β also regulates the expression of genes associated with stem/progenitor cells, which indicates that HNF1β may play an important role in stem cell regulation. In this review, we discuss some of the current developments about HNF1β and tumor, the relationship between HNF1β and stem/progenitor cells, and the potential pathogenesis of HNF1β in various tumors.

Tài liệu tham khảo

Azmi AS, Bao GW, Gao J, Mohammad RM, Sarkar FH. Network insights into the genes regulated by hepatocyte nuclear factor 4 in response to drug induced perturbations: a review. Curr Drug Discov Technol. 2013;10(2):147–54. Mendel DB, Hansen LP, Graves MK, Conley PB, Crabtree GR. HNF-1 alpha and HNF-1 beta (vHNF-1) share dimerization and homeo domains, but not activation domains, and form heterodimers in vitro. Genes Dev. 1991;5(6):1042–56. Yang JY, Hung MC. Deciphering the role of forkhead transcription factors in cancer therapy. Curr Drug Targets. 2011;12(9):1284–90. Watt AJ, Garrison WD, Duncan SA. HNF4: a central regulator of hepatocyte differentiation and function. Hepatology. 2003;37(6):1249–53. Wang K, Holterman AX. Pathophysiologic role of hepatocyte nuclear factor 6. Cell Signal. 2012;24(1):9–16. Gudmundsson J, Sulem P, Steinthorsdottir V, Bergthorsson JT, Thorleifsson G, Manolescu A, Rafnar T, Gudbjartsson D, Agnarsson BA, Baker A, et al. Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nat Genet. 2007;39(8):977–83. Horikawa Y, Iwasaki N, Hara M, Furuta H, Hinokio Y, Cockburn BN, Lindner T, Yamagata K, Ogata M, Tomonaga O, et al. Mutation in hepatocyte nuclear factor-1 beta gene (TCF2) associated with MODY. Nat Genet. 1997;17(4):384–5. Brimo F, Herawi M, Sharma R, Netto GJ, Epstein JI, Illei PB. Hepatocyte nuclear factor-1beta expression in clear cell adenocarcinomas of the bladder and urethra: diagnostic utility and implications for histogenesis. Hum Pathol. 2011;42(11):1613–9. Edghill EL, Bingham C, Ellard S, Hattersley AT. Mutations in hepatocyte nuclear factor-1beta and their related phenotypes. J Med Genet. 2006;43(1):84–90. Coffinier C, Gresh L, Fiette L, Tronche F, Schutz G, Babinet C, Pontoglio M, Yaniv M, Barra J. Bile system morphogenesis defects and liver dysfunction upon targeted deletion of HNF1beta. Development. 2002;129(8):1829–38. Ninomiya T, Hayashi Y, Saijoh K, Ohta K, Yoon S, Nakabayashi H, Tamaoki T, Kasuga M, Itoh H. Expression ratio of hepatocyte nuclear factor-1 to variant hepatocyte nuclear factor-1 in differentiation of hepatocellular carcinoma and hepatoblastoma. J Hepatol. 1996;25(4):445–53. Wang W, Hayashi Y, Ninomiya T, Ohta K, Nakabayashi H, Tamaoki T, Itoh H. Expression of HNF-1 alpha and HNF-1 beta in various histological differentiations of hepatocellular carcinoma. J Pathol. 1998;184(3):272–8. Shim JH, Lee HC, Han S, Kang HJ, Yu E, Lee SG. Hepatocyte nuclear factor 1beta is a novel prognostic marker independent of the Milan criteria in transplantable hepatocellular carcinoma: a retrospective analysis based on tissue microarrays. Liver transplant Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc. 2013;19(3):336–45. Tanaka T, Tomaru Y, Nomura Y, Miura H, Suzuki M, Hayashizaki Y. Comprehensive search for HNF-1beta-regulated genes in mouse hepatoma cells perturbed by transcription regulatory factor-targeted RNAi. Nucleic Acids Res. 2004;32(9):2740–50. Mazur PK, Riener MO, Jochum W, Kristiansen G, Weber A, Schmid RM, Siveke JT. Expression and clinicopathological significance of notch signaling and cell-fate genes in biliary tract cancer. Am J Gastroenterol. 2012;107(1):126–35. Kim L, Liao J, Zhang M, Talamonti M, Bentrem D, Rao S, Yang GY. Clear cell carcinoma of the pancreas: histopathologic features and a unique biomarker: hepatocyte nuclear factor-1beta. Mod Pathol Off J US Can Acad Pathol Inc. 2008;21(9):1075–83. Silva TD, Vidigal VM, Felipe AV, De Lima JM, Neto RA, Saad SS, Forones NM. DNA methylation as an epigenetic biomarker in colorectal cancer. Oncol Lett. 2013;6(6):1687–92. Buchner A, Castro M, Hennig A, Popp T, Assmann G, Stief CG, Zimmermann W. Downregulation of HNF-1B in renal cell carcinoma is associated with tumor progression and poor prognosis. Urology. 2010;76(2):507 (e506–511). Wang CC, Mao TL, Yang WC, Jeng YM. Underexpression of hepatocyte nuclear factor-1beta in chromophobe renal cell carcinoma. Histopathology. 2013;62(4):589–94. Rebouissou S, Vasiliu V, Thomas C, Bellanne-Chantelot C, Bui H, Chretien Y, Timsit J, Rosty C, Laurent-Puig P, Chauveau D, et al. Germline hepatocyte nuclear factor 1alpha and 1beta mutations in renal cell carcinomas. Hum Mol Genet. 2005;14(5):603–14. Gad S, Lefevre SH, Khoo SK, Giraud S, Vieillefond A, Vasiliu V, Ferlicot S, Molinie V, Denoux Y, Thiounn N, et al. Mutations in BHD and TP53 genes, but not in HNF1beta gene, in a large series of sporadic chromophobe renal cell carcinoma. Br J Cancer. 2007;96(2):336–40. Szponar A, Yusenko MV, Kuiper R, van Kessel AG, Kovacs G. Genomic profiling of papillary renal cell tumours identifies small regions of DNA alterations: a possible role of HNF1B in tumour development. Histopathology. 2011;58(6):934–43. Young RH, Scully RE. Clear cell adenocarcinoma of the bladder and urethra. A report of three cases and review of the literature. Am J Surg Pathol. 1985;9(11):816–26. Eeles RA, Kote-Jarai Z, Giles GG, Olama AA, Guy M, Jugurnauth SK, Mulholland S, Leongamornlert DA, Edwards SM, Morrison J, et al. Multiple newly identified loci associated with prostate cancer susceptibility. Nat Genet. 2008;40(3):316–21. Thomas G, Jacobs KB, Yeager M, Kraft P, Wacholder S, Orr N, Yu K, Chatterjee N, Welch R, Hutchinson A, et al. Multiple loci identified in a genome-wide association study of prostate cancer. Nat Genet. 2008;40(3):310–5. Sun J, Zheng SL, Wiklund F, Isaacs SD, Purcell LD, Gao Z, Hsu FC, Kim ST, Liu W, Zhu Y, et al. Evidence for two independent prostate cancer risk-associated loci in the HNF1B gene at 17q12. Nat Genet. 2008;40(10):1153–5. Berndt SI, Sampson J, Yeager M, Jacobs KB, Wang Z, Hutchinson A, Chung C, Orr N, Wacholder S, Chatterjee N, et al. Large-scale fine mapping of the HNF1B locus and prostate cancer risk. Hum Mol Genet. 2011;20(16):3322–9. Zhang YR, Xu Y, Yang K, Liu M, Wei D, Zhang YG, Shi XH, Wang JY, Yang F, Wang X, et al. Association of six susceptibility Loci with prostate cancer in northern chinese men. Asian Pac J Cancer Prev APJCP. 2012;13(12):6273–6. Hu YL, Zhong D, Pang F, Ning QY, Zhang YY, Li G, Wu JZ, Mo ZN. HNF1b is involved in prostate cancer risk via modulating androgenic hormone effects and coordination with other genes. Genet Mol Res GMR. 2013;12(2):1327–35. Tsuchiya A, Sakamoto M, Yasuda J, Chuma M, Ohta T, Ohki M, Yasugi T, Taketani Y, Hirohashi S. Expression profiling in ovarian clear cell carcinoma: identification of hepatocyte nuclear factor-1 beta as a molecular marker and a possible molecular target for therapy of ovarian clear cell carcinoma. Am J Pathol. 2003;163(6):2503–12. Yamamoto S, Tsuda H, Aida S, Shimazaki H, Tamai S, Matsubara O. Immunohistochemical detection of hepatocyte nuclear factor 1beta in ovarian and endometrial clear-cell adenocarcinomas and nonneoplastic endometrium. Hum Pathol. 2007;38(7):1074–80. Kao YC, Lin MC, Lin WC, Jeng YM, Mao TL. Utility of hepatocyte nuclear factor-1beta as a diagnostic marker in ovarian carcinomas with clear cells. Histopathology. 2012;61(5):760–8. Okamoto T, Mandai M, Matsumura N, Yamaguchi K, Kondoh H, Amano Y, Baba T, Hamanishi J, Abiko K, Kosaka K, et al. Hepatocyte nuclear factor-1beta (HNF-1beta) promotes glucose uptake and glycolytic activity in ovarian clear cell carcinoma. Mol Carcinog. 2015;54(1):35–49. Li J, Zhang Y, Gao Y, Cui Y, Liu H, Li M, Tian Y. Downregulation of HNF1 homeobox B is associated with drug resistance in ovarian cancer. Oncol Rep. 2014;32:979–88. Terasawa K, Toyota M, Sagae S, Ogi K, Suzuki H, Sonoda T, Akino K, Maruyama R, Nishikawa N, Imai K, et al. Epigenetic inactivation of TCF2 in ovarian cancer and various cancer cell lines. Br J Cancer. 2006;94(6):914–21. Shen H, Fridley BL, Song H, Lawrenson K, Cunningham JM, Ramus SJ, Cicek MS, Tyrer J, Stram D, Larson MC, et al. Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer. Nat Commun. 2013;4:1628. Spurdle AB, Thompson DJ, Ahmed S, Ferguson K, Healey CS, O’Mara T, Walker LC, Montgomery SB, Dermitzakis ET, Australian National Endometrial Cancer Study G, et al. Genome-wide association study identifies a common variant associated with risk of endometrial cancer. Nat Genet. 2011;43(5):451–4. Setiawan VW, Haessler J, Schumacher F, Cote ML, Deelman E, Fesinmeyer MD, Henderson BE, Jackson RD, Vockler JS, Wilkens LR, et al. HNF1B and endometrial cancer risk: results from the PAGE study. PLoS One. 2012;7(1):e30390. De Vivo I, Prescott J, Setiawan VW, Olson SH, Wentzensen N, Australian National Endometrial Cancer Study G, Attia J, Black A, Brinton L, Chen C et al. Genome-wide association study of endometrial cancer in E2C2. Hum Genet. 2014;133(2):211–24. Fadare O, Liang SX. Diagnostic utility of hepatocyte nuclear factor 1-beta immunoreactivity in endometrial carcinomas: lack of specificity for endometrial clear cell carcinoma. Appl Immunohistochem Mol Morphol AIMM/Off Publ Soc Appl Immunohistochem. 2012;20(6):580–7. Kato N, Tamura G, Motoyama T. Hypomethylation of hepatocyte nuclear factor-1beta (HNF-1beta) CpG island in clear cell carcinoma of the ovary. Virchows Arch Int J Pathol. 2008;452(2):175–80. Tommasi S, Karm DL, Wu X, Yen Y, Pfeifer GP. Methylation of homeobox genes is a frequent and early epigenetic event in breast cancer. Breast Cancer Res BCR. 2009;11(1):R14. Senkel S, Lucas B, Klein-Hitpass L, Ryffel GU. Identification of target genes of the transcription factor HNF1beta and HNF1alpha in a human embryonic kidney cell line. Biochim Biophys Acta. 2005;1731(3):179–90. Kato N, Motoyama T. Overexpression of osteopontin in clear cell carcinoma of the ovary: close association with HNF-1beta expression. Histopathology. 2008;52(6):682–8. Rangaswami H, Bulbule A, Kundu GC. Osteopontin: role in cell signaling and cancer progression. Trends Cell Biol. 2006;16(2):79–87. Shigetomi H, Higashiura Y, Kajihara H, Kobayashi H. Targeted molecular therapies for ovarian cancer: an update and future perspectives (Review). Oncol Rep. 2012;28(2):395–408. Morgan MA, Parsels LA, Zhao L, Parsels JD, Davis MA, Hassan MC, Arumugarajah S, Hylander-Gans L, Morosini D, Simeone DM, et al. Mechanism of radiosensitization by the Chk1/2 inhibitor AZD7762 involves abrogation of the G2 checkpoint and inhibition of homologous recombinational DNA repair. Cancer Res. 2010;70(12):4972–81. Yamada Y, Shigetomi H, Onogi A, Haruta S, Kawaguchi R, Yoshida S, Furukawa N, Nagai A, Tanase Y, Tsunemi T, et al. Redox-active iron-induced oxidative stress in the pathogenesis of clear cell carcinoma of the ovary. Int J Gynecol Cancer Off J Int Gynecol Cancer Soc. 2011;21(7):1200–7. Masur K, Schwartz F, Entschladen F, Niggemann B, Zaenker KS. DPPIV inhibitors extend GLP-2 mediated tumour promoting effects on intestinal cancer cells. Regul Pept. 2006;137(3):147–55. Kuk C, Gunawardana CG, Soosaipillai A, Kobayashi H, Li L, Zheng Y, Diamandis EP. Nidogen-2: a new serum biomarker for ovarian cancer. Clin Biochem. 2010;43(4–5):355–61. Kajihara H, Yamada Y, Kanayama S, Furukawa N, Noguchi T, Haruta S, Yoshida S, Sado T, Oi H, Kobayashi H. Clear cell carcinoma of the ovary: potential pathogenic mechanisms (Review). Oncol Rep. 2010;23(5):1193–203. Akasaka J, Uekuri C, Shigetomi H, Koike M, Kobayashi H. Hepatocyte nuclear factor (HNF)-1beta and its physiological importance in endometriosis. Biomed Rep. 2013;1(1):13–7. Hatzis P, Talianidis I. Regulatory mechanisms controlling human hepatocyte nuclear factor 4 alpha gene expression. Mol Cell Biol. 2001;21(21):7320–30. Fabris L, Cadamuro M, Guido M, Spirli C, Fiorotto R, Colledan M, Torre G, Alberti D, Sonzogni A, Okolicsanyi L, et al. Analysis of liver repair mechanisms in Alagille syndrome and biliary atresia reveals a role for notch signaling. Am J Pathol. 2007;171(2):641–53. Zhou ZC, Dong QG, Fu DL, Gong YY, Ni QX. Characteristics of Notch2(+) pancreatic cancer stem-like cells and the relationship with centroacinar cells. Cell Biol Int. 2013;37(8):805–11. Charafe-Jauffret E, Ginestier C, Iovino F, Wicinski J, Cervera N, Finetti P, Hur MH, Diebel ME, Monville F, Dutcher J, et al. Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature. Cancer Res. 2009;69(4):1302–13. Strazzabosco M, Fabris L. Notch signaling in hepatocellular carcinoma: guilty in association! Gastroenterology. 2012;143(6):1430–4. Jaggupilli A, Elkord E. Significance of CD44 and CD24 as cancer stem cell markers: an enduring ambiguity. Clin Dev Immunol. 2012;2012:708036. Matheu A, Collado M, Wise C, Manterola L, Cekaite L, Tye AJ, Canamero M, Bujanda L, Schedl A, Cheah KS, et al. Oncogenicity of the developmental transcription factor Sox9. Cancer Res. 2012;72(5):1301–15. Coombes JD, Swiderska-Syn M, Dolle L, Reid D, Eksteen B, Claridge L, Briones-Orta MA, Shetty S, Oo YH, Riva A, et al. Osteopontin neutralisation abrogates the liver progenitor cell response and fibrogenesis in mice. Gut. 2015;64(7):1120–31. Luo Z, Wu RR, Lv L, Li P, Zhang LY, Hao QL, Li W. Prognostic value of CD44 expression in non-small cell lung cancer: a systematic review. Int J Clin Exp Pathol. 2014;7(7):3632–46. Rodrigo-Torres D, Affo S, Coll M, Morales-Ibanez O, Millan C, Blaya D, Alvarez-Guaita A, Rentero C, Lozano JJ, Maestro MA, et al. The biliary epithelium gives rise to liver progenitor cells. Hepatology. 2014;60(4):1367–77. Yu B, He ZY, You P, Han QW, Xiang D, Chen F, Wang MJ, Liu CC, Lin XW, Borjigin U, et al. Reprogramming fibroblasts into bipotential hepatic stem cells by defined factors. Cell Stem Cell. 2013;13(3):328–40. Pan FC, Bankaitis ED, Boyer D, Xu X, Van de Casteele M, Magnuson MA, Heimberg H, Wright CV. Spatiotemporal patterns of multipotentiality in Ptf1a-expressing cells during pancreas organogenesis and injury-induced facultative restoration. Development. 2013;140(4):751–64. Lynn FC, Smith SB, Wilson ME, Yang KY, Nekrep N, German MS. Sox9 coordinates a transcriptional network in pancreatic progenitor cells. Proc Natl Acad Sci USA. 2007;104(25):10500–5. Hattersley AT, Pearson ER. Minireview: pharmacogenetics and beyond: the interaction of therapeutic response, beta-cell physiology, and genetics in diabetes. Endocrinology. 2006;147(6):2657–63. Poll AV, Pierreux CE, Lokmane L, Haumaitre C, Achouri Y, Jacquemin P, Rousseau GG, Cereghini S, Lemaigre FP. A vHNF1/TCF2-HNF6 cascade regulates the transcription factor network that controls generation of pancreatic precursor cells. Diabetes. 2006;55(1):61–9. Oliver-Krasinski JM, Kasner MT, Yang J, Crutchlow MF, Rustgi AK, Kaestner KH, Stoffers DA. The diabetes gene Pdx1 regulates the transcriptional network of pancreatic endocrine progenitor cells in mice. J Clin Investig. 2009;119(7):1888–98.