Forkhead box protein A1 (FOXA1), also known as hepatocyte nuclear factor 3-alpha (HNF-3A), is a protein that in humans is encoded by the FOXA1gene.[1][2][3]
FOXA1 is a member of the forkhead class of DNA-binding proteins. These hepatocyte nuclear factors are transcriptional activators for liver-specific transcripts such as albumin and transthyretin, and they also interact with chromatin as a pioneer factor. Similar family members in mice have roles in the regulation of metabolism and in the differentiation of the pancreas and liver.[1]
Marker in breast cancer
FOXA1 in breast cancer is highly correlated with ERα+, GATA3+, and PR+protein expression as well as endocrine signaling. FOXA1 acts as a pioneer factor for ERa in ERα+ breast cancer, and its expression might identify ERα+ cancers that undergo rapid reprogramming of ERa signaling that is associated with poor outcomes and treatment resistance.[4] Conversely, in ERα− breast cancer FOXA1 is highly correlated with low-grade morphology and improved disease free survival. FOXA1 is a downstream target of GATA3 in the mammary gland.[5] Expression in ERα− cancers may identify a subset of tumors that is responsive to other endocrine therapies such as androgen receptor antagonist treatment.[6][7]
Role in prostate cancer
Mutations in this gene have been recurrently seen in instances of prostate cancer.[8]
↑Bingle CD, Gowan S (1996). "Molecular cloning of the forkhead transcription factor HNF-3 alpha from a human pulmonary adenocarcinoma cell line". Biochim Biophys Acta. 1307 (1): 17–20. doi:10.1016/0167-4781(96)00058-9. PMID8652662.
↑Mincheva A, Lichter P, Schütz G, Kaestner KH (1997). "Assignment of the human genes for hepatocyte nuclear factor 3-alpha, -beta, and -gamma (HNF3A, HNF3B, HNF3G) to 14q12-q13, 20p11, and 19q13.2-q13.4". Genomics. 39 (3): 417–9. doi:10.1006/geno.1996.4477. PMID9119385.
↑Barbieri CE, Baca SC, Lawrence MS, Demichelis F, Blattner M, Theurillat JP, White TA, Stojanov P, Van Allen E, Stransky N, Nickerson E, Chae SS, Boysen G, Auclair D, Onofrio RC, Park K, Kitabayashi N, MacDonald TY, Sheikh K, Vuong T, Guiducci C, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Hussain WM, Ramos AH, Winckler W, Redman MC, Ardlie K, Tewari AK, Mosquera JM, Rupp N, Wild PJ, Moch H, Morrissey C, Nelson PS, Kantoff PW, Gabriel SB, Golub TR, Meyerson M, Lander ES, Getz G, Rubin MA, Garraway LA (June 2012). "Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer". Nat. Genet. 44 (6): 685–9. doi:10.1038/ng.2279. PMC3673022. PMID22610119.
Further reading
Song L, Xu Z, Zhang C, et al. (2009). "Up-regulation of the HSP72 by Foxa1 in MCF-7 human breast cancer cell line". Biochem. Biophys. Res. Commun. 386 (1): 30–4. doi:10.1016/j.bbrc.2009.05.120. PMID19486887.
Liu N, Niu Y, Wang SL, et al. (2010). "[Diagnostic and prognostic significance of FOXA1 expression in molecular subtypes of breast invasive ductal carcinomas]". Zhonghua Yi Xue Za Zhi. 90 (20): 1403–7. PMID20646630.
Nakshatri H, Badve S (2007). "FOXA1 as a therapeutic target for breast cancer". Expert Opin. Ther. Targets. 11 (4): 507–14. doi:10.1517/14728222.11.4.507. PMID17373880.
Iacobazzi V, Infantino V, Bisaccia F, et al. (2009). "Role of FOXA in mitochondrial citrate carrier gene expression and insulin secretion". Biochem. Biophys. Res. Commun. 385 (2): 220–4. doi:10.1016/j.bbrc.2009.05.030. PMID19445897.
Nucera C, Eeckhoute J, Finn S, et al. (2009). "FOXA1 is a potential oncogene in anaplastic thyroid carcinoma". Clin. Cancer Res. 15 (11): 3680–9. doi:10.1158/1078-0432.CCR-08-3155. PMID19470727.
Lee HJ, Chattopadhyay S, Yoon WH, et al. (2010). "Overexpression of hepatocyte nuclear factor-3alpha induces apoptosis through the upregulation and accumulation of cytoplasmic p53 in prostate cancer cells". Prostate. 70 (4): 353–61. doi:10.1002/pros.21069. PMID19866472.
Huang QY, Li GH, Kung AW (2009). "The -9247 T/C polymorphism in the SOST upstream regulatory region that potentially affects C/EBPalpha and FOXA1 binding is associated with osteoporosis". Bone. 45 (2): 289–94. doi:10.1016/j.bone.2009.03.676. PMID19371798.
Sano M, Aoyagi K, Takahashi H, et al. (2010). "Forkhead box A1 transcriptional pathway in KRT7-expressing esophageal squamous cell carcinomas with extensive lymph node metastasis". Int. J. Oncol. 36 (2): 321–30. doi:10.3892/ijo_00000503. PMID20043065.