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.[5][6][7]
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.[5]
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.[8] 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.[9] Expression in ERα− cancers may identify a subset of tumors that is responsive to other endocrine therapies such as androgen receptor antagonist treatment.[10][11]
^Bingle CD, Gowan S (June 1996). "Molecular cloning of the forkhead transcription factor HNF-3 alpha from a human pulmonary adenocarcinoma cell line". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1307 (1): 17–20. doi:10.1016/0167-4781(96)00058-9. PMID8652662.
^Mincheva A, Lichter P, Schütz G, Kaestner KH (February 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): 417–419. doi:10.1006/geno.1996.4477. PMID9119385.
^BenAyed-Guerfali D, Dabbèche-Bouricha E, Ayadi W, Trifa F, Charfi S, Khabir A, et al. (June 2019). "Association of FOXA1 and EMT markers (Twist1 and E-cadherin) in breast cancer". Molecular Biology Reports. 46 (3): 3247–3255. doi:10.1007/s11033-019-04784-w. PMID30941644. S2CID91190545.
Song L, Xu Z, Zhang C, Qiao X, Huang C (August 2009). "Up-regulation of the HSP72 by Foxa1 in MCF-7 human breast cancer cell line". Biochemical and Biophysical Research Communications. 386 (1): 30–34. doi:10.1016/j.bbrc.2009.05.120. PMID19486887.
Liu N, Niu Y, Wang SL, Yu Q, Zhang RJ, Liu TJ (May 2010). "[Diagnostic and prognostic significance of FOXA1 expression in molecular subtypes of breast invasive ductal carcinomas]". Zhonghua Yi Xue Za Zhi. 90 (20): 1403–1407. PMID20646630.
Iacobazzi V, Infantino V, Bisaccia F, Castegna A, Palmieri F (July 2009). "Role of FOXA in mitochondrial citrate carrier gene expression and insulin secretion". Biochemical and Biophysical Research Communications. 385 (2): 220–224. doi:10.1016/j.bbrc.2009.05.030. hdl:11586/126284. PMID19445897.
Lee HJ, Chattopadhyay S, Yoon WH, Bahk JY, Kim TH, Kang HS, Lee K (March 2010). "Overexpression of hepatocyte nuclear factor-3alpha induces apoptosis through the upregulation and accumulation of cytoplasmic p53 in prostate cancer cells". The Prostate. 70 (4): 353–361. doi:10.1002/pros.21069. PMID19866472. S2CID20375911.
Huang QY, Li GH, Kung AW (August 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): 289–294. doi:10.1016/j.bone.2009.03.676. PMID19371798.