FOXA1 promotes tumor cell proliferation through AR involving the Notch pathway in endometrial cancer

详细信息    查看全文

• 作者：Meiting Qiu (3)
  Wei Bao (3)
  Jingyun Wang (3)
  Tingting Yang (3)
  Xiaoying He (3)
  Yun Liao (3)
  Xiaoping Wan (3)
  
• 关键词：Endometrial cancer ; FOXA1 ; AR ; Proliferation ; Notch pathway
• 刊名：BMC Cancer
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：14
• 期：1
• 全文大小：2,083 KB
• 参考文献：1. Bokhman JV: Two pathogenetic types of endometrial carcinoma. / Gynecol Oncol 1983, 15:10-7. CrossRef
  2. Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H, Robertson AG, Pashtan I, Shen R, Benz CC, Yau C, Laird PW, Ding L, Zhang W, Mills GB, Kucherlapati R, Mardis ER, Levine DA, Cancer Genome Atlas Research Network: Integrated genomic characterization of endometrial carcinoma. / Nature 2013, 497:67-3. CrossRef
  3. Gadducci A, Cosio S, Genazzani AR: Old and new perspectives in the pharmacological treatment of advanced or recurrent endometrial cancer: Hormonal therapy, chemotherapy and molecularly targeted therapies. / Crit Rev Oncol Hematol 2006, 58:242-56. CrossRef
  4. Ito K, Suzuki T, Akahira J, Moriya T, Kaneko C, Utsunomiya H, Yaegashi N, Okamura K, Sasano H: Expression of androgen receptor and 5α-reductases in the human normal endometrium and it’s disorders. / Int J Cancer 2002, 99:652-57. CrossRef
  5. Horie K, Takakura K, Imai K, Liao S, Mori T: Immunohistochemical localization of androgen receptor in the human endometrium, decidua, placenta and pathological conditions of the endometrium. / Hum Reprod 1992, 7:1461-466.
  6. Hu YC, Wang PH, Yeh S, Wang RS, Xie C, Xu Q, Zhou X, Chao HT, Tsai MY, Chang C: Subfertility and defective folliculogenesis in female mice lacking androgen receptor. / Proc Natl Acad Sci USA 2004, 101:11209-1214. CrossRef
  7. Carlsson P, Mahlapuu M: Forkhead transcription factors: key players in development and metabolism. / Dev Biol 2002, 250:1-3. CrossRef
  8. Kaestner KH: The FoxA factors in organogenesis and differentiation. / Curr Opin Genet Dev 2010, 20:527-32. CrossRef
  9. Lupien M, Eeckhoute J, Meyer CA, Wang Q, Zhang Y, Li W, Carroll JS, Liu XS, Brown M: FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription. / Cell 2008, 132:958-70. CrossRef
  10. Gao N, Zhang J, Rao MA, Case TC, Mirosevich J, Wang Y, Jin R, Gupta A, Rennie PS, Matusik RJ: The role of hepatocyte nuclear factor-3 alpha (Forkhead Box A1) and androgen receptor in transcriptional regulation of prostatic genes. / Mol Endocrinol 2003, 17:1484-507. CrossRef
  11. Sahu B, Laakso M, Ovaska K, Mirtti T, Lundin J, Rannikko A, Sankila A, Turunen JP, Lundin M, Konsti J, Vesterinen T, Nordling S, Kallioniemi O, Hautaniemi S, J?nne OA: Dual role of FoxA1 in androgen receptor binding to chromatin, androgen signalling and prostate cancer. / EMBO J 2011, 30:3962-976. CrossRef
  12. Robinson JL, Macarthur S, Ross-Innes CS, Tilley WD, Neal DE, Mills IG, Carroll JS: Androgen receptor driven transcription in molecular apocrine breast cancer is mediated by FoxA1. / EMBO J 2011, 30:3019-027. CrossRef
  13. Axelson H: Notch signaling and cancer: emerging complexity. / Semin Cancer Biol 2004, 14:317-19. CrossRef
  14. Qiao L, Wong BC: Role of Notch signaling in colorectal cancer. / Carcinogenesis 2009, 30:1979-986. CrossRef
  15. Rose SL: Notch signaling pathway in ovarian cancer. / Int J Gynecol Cancer 2009, 19:564-66. CrossRef
  16. De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, Mumm JS, Schroeter EH, Schrijvers V, Wolfe MS, Ray WJ, Goate A, Kopan R: A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. / Nature 1999, 398:518-22. CrossRef
  17. Wei Y, Zhang Z, Liao H, Wu L, Wu X, Zhou D, Xi X, Zhu Y, Feng Y: Nuclear estrogen receptor-mediated Notch signaling and GPR30-mediated PI3K/AKT signaling in the regulation of endometrial cancer cell proliferation. / Oncol Rep 2012, 27:504-10.
  18. Bao W, Wang HH, Tian FJ, He XY, Qiu MT, Wang JY, Zhang HJ, Wang LH, Wan XP: A TrkB-STAT3-miR-204-p regulatory circuitry controls proliferation and invasion of endometrial carcinoma cells. / Mol Cancer 2013, 12:155. CrossRef
  19. Ni M, Chen Y, Fei T, Li D, Lim E, Liu XS, Brown M: Amplitude modulation of androgen signaling by c-MYC. / Genes Dev 2013, 27:734-48. CrossRef
  20. Yazawa T, Kawabe S, Kanno M, Mizutani T, Imamichi Y, Ju Y, Matsumura T, Yamazaki Y, Usami Y, Kuribayashi M, Shimada M, Kitano T, Umezawa A, Miyamoto K: Androgen/androgen receptor pathway regulates expression of the genes for cyclooxygenase-2 and amphiregulin in periovulatory granulosa cells. / Mol Cell Endocrinol 2013, 369:42-1. CrossRef
  21. Yoshida K, He PJ, Yamauchi N, Hashimoto S, Hattori MA: Up-regulation of circadian clock gene Period 2 in the prostate mesenchymal cells during flutamide-induced apoptosis. / Mol Cell Biochem 2010, 335:37-5. CrossRef
  22. Li Z, Tuteja G, Schug J, Kaestner KH: Foxa1 and Foxa2 are essential for sexual dimorphism in liver cancer. / Cell 2012, 148:72-3. CrossRef
  23. Dai R, Yan D, Li J, Chen S, Liu Y, Chen R, Duan C, Wei M, Li H, He T: Activation of PKR/eIF2α signaling cascade is associated with dihydrotestosterone-induced cell cycle arrest and apoptosis in human liver cells. / J Cell Biochem 2012, 113:1800-808. CrossRef
  24. Lin L, Miller CT, Contreras JI, Prescott MS, Dagenais SL, Wu R, Yee J, Orringer MB, Misek DE, Hanash SM, Glover TW, Beer DG: The hepatocyte nuclear factor 3 alpha gene, HNF3alpha (FOXA1), on chromosome band 14q13 is amplified and overexpressed in esophageal and lung adenocarcinomas. / Cancer Res 2002, 62:5273-279.
  25. Jain RK, Mehta RJ, Nakshatri H, Idrees MT, Badve SS: High-level expression of forkhead-box protein A1 in metastatic prostate cancer. / Histopathology 2011, 58:766-72. CrossRef
  26. Coulouarn C, Factor VM, Andersen JB, Durkin ME, Thorgeirsson SS: Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. / Oncogene 2009, 28:3526-536. CrossRef
  27. Song Y, Washington MK, Crawford HC: Loss of FOXA1/2 is essential for the epithelial-to-mesenchymal transition in pancreatic cancer. / Cancer Res 2010, 70:2115-125. CrossRef
  28. Hurtado A, Holmes KA, Ross-Innes CS, Schmidt D, Carroll JS: FOXA1 is a key determinant of estrogen receptor function and endocrine response. / Nat Genet 2011, 43:27-3. CrossRef
  29. Sano M, Aoyagi K, Takahashi H, Kawamura T, Mabuchi T, Igaki H, Tachimori Y, Kato H, Ochiai A, Honda H, Nimura Y, Nagino M, Yoshida T, Sasaki H: Forkhead box A1 transcriptional pathway in KRT7-expressing esophageal squamous cell carcinomas with extensive lymph node metastasis. / Int J Oncol 2010, 36:321-30.
  30. Nucera C, Eeckhoute J, Finn S, Carroll JS, Ligon AH, Priolo C, Fadda G, Toner M, Sheils O, Attard M, Pontecorvi A, Nose V, Loda M, Brown M: FOXA1 is a potential oncogene in anaplastic thyroid carcinoma. / Clin Cancer Res 2009, 15:3680-689. CrossRef
  31. Abe Y, Ijichi N, Ikeda K, Kayano H, Horie-Inoue K, Takeda S, Inoue S: Forkhead box transcription factor, forkhead box A1, shows negative association with lymph node status in endometrial cancer, and represses cell proliferation and migration of endometrial cancer cells. / Cancer Sci 2012, 103:806-12. CrossRef
  32. De Marco P, Bartella V, Vivacqua A, Lappano R, Santolla MF, Morcavallo A, Pezzi V, Belfiore A, Maggiolini M: Insulin-like growth factor-I regulates GPER expression and function in cancer cells. / Oncogene 2013, 32:678-88. CrossRef
  33. Hackenberg R, Hawighorst T, Hild F, Schulz KD: Establishment of new epithelial carcinoma cell lines by blocking monolayer formation. / J Cancer Res Clin Oncol 1997, 123:669-73. CrossRef
  34. Jiang F, Liu T, He Y, Yan Q, Chen X, Wang H, Wan X: MiR-125b promotes proliferation and migration of type II endometrial carcinoma cells through targeting TP53INP1 tumor suppressor in vitro and in vivo. / BMC Cancer 2011, 11:425. CrossRef
  35. Sisci D, Maris P, Cesario MG, Anselmo W, Coroniti R, Trombino GE, Romeo F, Ferraro A, Lanzino M, Aquila S, Maggiolini M, Mauro L, Morelli C, Andò S: The estrogen receptor α is the key regulator of the bifunctional role of FoxO3a transcription factor in breast cancer motility and invasiveness. / Cell Cycle 2013, 12:3405-420. CrossRef
  36. Jongen VH, Sluijmer AV, Heineman MJ: The postmenopausal ovary as an androgen-producing gland; hypothesis on the etiology of endometrial cancer. / Maturitas 2002, 43:77-5. CrossRef
  37. Sasaki M, Sakuragi N, Dahiya R: The CAG repeats in exon 1 of the androgen receptor gene are significantly longer in endometrial cancer patients. / Biochem Biophys Res Commun 2003, 305:1105-108. CrossRef
  38. Sahlin L, Norstedt G, Eriksson H: Androgen regulation of the insulin-like growth factor-I and the estrogen receptor in rat uterus and liver. / J Steroid Biochem Mol Biol 1994, 51:57-6. CrossRef
  39. Cirillo LA, Zaret KS: An early developmental transcription factor complex that is more stable on nucleosome core particles than on free DNA. / Mol Cell 1999, 4:961-69. CrossRef
  40. Laganière J, Deblois G, Lefebvre C, Bataille AR, Robert F, Giguère V: From the Cover: location analysis of estrogen receptor alpha target promoters reveals that FOXA1 defines a domain of the estrogen response. / Proc Natl Acad Sci U S A 2005, 102:11651-1656. CrossRef
  41. Jia L, Landan G, Pomerantz M, Jaschek R, Herman P, Reich D, Yan C, Khalid O, Kantoff P, Oh W, Manak JR, Berman BP, Henderson BE, Frenkel B, Haiman CA, Freedman M, Tanay A, Coetzee GA: Functional enhancers at the gene-poor 8q24 cancer-linked locus. / PLoS Genet 2009, 5:e1000597. CrossRef
  42. Zang S, Ji Ch QX, Dong X, Ma D, Ye J, Ma R, Dai J, Guo D: A study on Notch signaling in human breast cancer. / Neoplasma 2007, 54:304-10.
  43. Wang Z, Zhang Y, Li Y, Banerjee S, Liao J, Sarkar FH: Down-regulation of Notch-1 contributes to cell growth inhibition and apoptosis in pancreatic cancer cells. / Mol Cancer Ther 2006, 5:483-93. CrossRef
  44. Zorn KK, Bonome T, Gangi L, Chandramouli GV, Awtrey CS, Gardner GJ, Barrett JC, Boyd J, Birrer MJ: Gene expression profiles of serous, endometrioid, and clear cell subtypes of ovarian and endometrial cancer. / Clin Cancer Res 2005, 11:6422-430. CrossRef
  45. Catalano S, Giordano C, Rizza P, Gu G, Barone I, Bonofiglio D, Giordano F, Malivindi R, Gaccione D, Lanzino M, De Amicis F, Andò S: Evidence that leptin through STAT and CREB signaling enhances cyclin D1 expression and promotes human endometrial cancer proliferation. / J Cell Physiol 2009, 218:490-00. CrossRef
  46. Rutanen EM, Nyman T, Lehtovirta P, Amm?l? M, Pekonen F: Suppressed expression of insulin-like growth factor binding protein-1 mRNA in the endometrium: a molecular mechanism associating endometrial cancer with its risk factors. / Int J Cancer 1994, 59:307-12. CrossRef
  47. Matsushima-Nishiu M, Unoki M, Ono K, Tsunoda T, Minaguchi T, Kuramoto H, Nishida M, Satoh T, Tanaka T, Nakamura Y: Growth and gene expression profile analyses of endometrial cancer cells expressing exogenous PTEN. / Cancer Res 2001, 61:3741-749.
  48. Huang KT, Pavlides SC, Lecanda J, Blank SV, Mittal KR, Gold LI: Estrogen and progesterone regulate p27kip1 levels via the ubiquitin-proteasome system: pathogenic and therapeutic implications for endometrial cancer. / PLoS One 2012, 7:e46072. CrossRef
  49. Thigpen T, Brady MF, Homesley HD, Soper JT, Bell J: Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. / J Clin Oncol 2001, 19:364-67.
  50. Day JM, Purohit A, Tutill HJ, Foster PA, Woo LW, Potter BV, Reed MJ: The development of steroid sulfatase inhibitors for hormone-dependent cancer therapy. / Ann N Y Acad Sci 2009, 1155:80-7. CrossRef
  51. The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1471-2407/14/78/prepub
  
• 作者单位：Meiting Qiu (3)
  Wei Bao (3)
  Jingyun Wang (3)
  Tingting Yang (3)
  Xiaoying He (3)
  Yun Liao (3)
  Xiaoping Wan (3)
  
  3. Department of Obstetrics and Gynecology, Shanghai First People’s Hospital, Shanghai Jiao Tong University School of Medicine, Xinsongjiang Road, Shanghai, China
  
• ISSN：1471-2407

文摘

Background Increasing evidence suggests that forkhead box A1 (FOXA1) is frequently dysregulated in many types of human cancers. However, the exact function and mechanism of FOXA1 in human endometrial cancer (EC) remains unclear. Methods FOXA1 expression, androgen receptor (AR) expression, and the relationships of these two markers with clinicopathological factors were determined by immunohistochemistry analysis. FOXA1 and AR were up-regulated by transient transfection with plasmids, and were down-regulated by transfection with siRNA or short hairpin RNA (shRNA). The effects of FOXA1 depletion and FOXA1 overexpression on AR-mediated transcription as well as Notch pathway and their impact on EC cell proliferation were examined by qRT-PCR, western blotting, co-immunoprecipitation, ChIP-PCR, MTT, colony-formation, and xenograft tumor–formation assays. Results We found that the expression of FOXA1 and AR in ECs was significantly higher than that in a typical hyperplasia and normal tissues. FOXA1 expression was significantly correlated with AR expression in clinical tissues. High FOXA1 levels positively correlated with pathological grade and depth of myometrial invasion in EC. High AR levels also positively correlated with pathological grade in EC. Moreover, the expression of XBP1, MYC, ZBTB16, and UHRF1, which are downstream targets of AR, was promoted by FOXA1 up-regulation or inhibited by FOXA1 down-regulation. Co-immunoprecipitation showed that FOXA1 interacted with AR in EC cells. ChIP-PCR assays showed that FOXA1 and AR could directly bind to the promoter and enhancer regions upstream of MYC. Mechanistic investigation revealed that over-expression of Notch1 and Hes1 proteins by FOXA1 could be reversed by AR depletion. In addition, we showed that down-regulation of AR attenuated FOXA1-up-regulated cell proliferation. However, AR didn’t influence the promotion effect of FOXA1 on cell migration and invasion. In vivo xenograft model, FOXA1 knockdown reduced the rate of tumor growth. Conclusions These results suggest that FOXA1 promotes cell proliferation by AR and activates Notch pathway. It indicated that FOXA1 and AR may serve as potential gene therapy in EC.