The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

FOXA1  -  forkhead box A1

Homo sapiens

Synonyms: Forkhead box protein A1, HNF-3-alpha, HNF-3A, HNF3A, Hepatocyte nuclear factor 3-alpha, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of FOXA1


High impact information on FOXA1

  • Further, FOXA1 was identified as a downstream target of GATA-3 in the mammary gland [5].
  • From the Cover: Location analysis of estrogen receptor alpha target promoters reveals that FOXA1 defines a domain of the estrogen response [6].
  • The promoters were linked to known ERalpha targets but also to many genes not directly associated with the estrogenic response, including the transcriptional factor FOXA1, whose expression correlates with the presence of ERalpha in breast tumors [6].
  • Taken together, these results define a paradigm for estrogen action in breast cancer cells and suggest that regulation of gene expression by nuclear receptors can be compartmentalized into unique transcriptional domains by means of licensing of their activity to cofactors such as FOXA1 [6].
  • Foxa-2 physically interacts with Akt, a key mediator of the phosphatidylinositol 3-kinase pathway and is phosphorylated at a single conserved site (T156) that is absent in Foxa-1 and Foxa-3 proteins [7].

Chemical compound and disease context of FOXA1

  • FOXA1, a winged-helix transcription factor belonging to the forkhead family, is one among them as it is expressed predominantly in luminal type A breast cancer, which is characterized by the presence of estrogen receptor-alpha (ERalpha) with favorable prognosis [8].
  • Foxa1 was strongly expressed in areas of prostatic intraepithelial neoplasia (PIN) in both the androgen dependent 12T-7f and in the metastatic, androgen independent 12T-10 LADY models [9].
  • FOXA1 expression correlates with luminal subtype A breast cancer and it is significant predictor of cancer-specific survival in patients with ER-positive tumors [10].

Biological context of FOXA1


Anatomical context of FOXA1

  • Forced expression of FOXA1 inhibited clonal growth of breast cancer cell lines, and FOXA1 levels inversely correlated with growth stimuli [1].
  • Hepatocyte nuclear factors 3 alpha, beta, and gamma (Foxa-1, -2, and -3) are transcriptional activators of important metabolic genes in the liver that are suppressed by the actions of insulin [7].
  • Foxa1 and Foxa2 cooperate to establish competence in foregut endoderm and are required for normal development of endoderm-derived organs such as the liver, pancreas, lungs, and prostate [12].
  • In post-natal life, members of the Foxa family control glucose metabolism through the regulation of multiple target genes in the liver, pancreas, and adipose tissue [12].
  • CONCLUSIONS: Foxa proteins represent epithelial cell markers in the murine prostate gland [13].

Associations of FOXA1 with chemical compounds

  • Specific Interactions of the Wing Domains of FOXA1 Transcription Factor with DNA [14].
  • The sequence immediately downstream of the AP-1 element contained a binding site for HNF-3 (FOXA), and simultaneous mutation of this site (fox-d) and an upstream FoxA binding site (-277, fox-u) caused a 4-fold reduction in chloramphenicol acetyltransferase activity [15].
  • To determine whether the wing domains contribute to stable DNA binding, we assessed complexes of FOXA with high and lower affinity DNA target sites by hydroxyl radical footprinting and site-directed mutagenesis [14].

Physical interactions of FOXA1

  • Mutation of the FOXA1 DNA-binding site in the p27(Kip1) promoter-luciferase construct significantly diminished the activity of FOXA1 alone or in combination with BRCA1 [11].

Regulatory relationships of FOXA1

  • The half-life of FOXA1 was increased when coexpressed with BRCA1 [11].
  • Restriction enzyme accessibility assays reveal that HNF3alpha promotes the assembly of an open chromatin structure at the AFP promoter [16].

Other interactions of FOXA1

  • Cotransfection of BRCA1 and FOXA1 resulted in a synergistic activation of the p27(Kip1) promoter [11].
  • Mutational analysis of the enhancer demonstrates that NF1/CTF cooperates with HNF3 alpha to induce enhancer activity [17].
  • Combined, these functional and structural data suggest that chromatin assembly establishes a barrier to block inappropriate expression of AFP in non-hepatic tissues and that tissue-specific factors, such as HNF3alpha, are required to alleviate the chromatin-mediated repression [16].

Analytical, diagnostic and therapeutic context of FOXA1


  1. FOXA1: Growth inhibitor and a favorable prognostic factor in human breast cancer. Wolf, I., Bose, S., Williamson, E.A., Miller, C.W., Karlan, B.Y., Koeffler, H.P. Int. J. Cancer (2007) [Pubmed]
  2. Human FOX gene family (Review). Katoh, M., Katoh, M. Int. J. Oncol. (2004) [Pubmed]
  3. The hepatocyte nuclear factor 3 alpha gene, HNF3alpha (FOXA1), on chromosome band 14q13 is amplified and overexpressed in esophageal and lung adenocarcinomas. Lin, L., Miller, C.T., Contreras, J.I., Prescott, M.S., Dagenais, S.L., Wu, R., Yee, J., Orringer, M.B., Misek, D.E., Hanash, S.M., Glover, T.W., Beer, D.G. Cancer Res. (2002) [Pubmed]
  4. FOXA1 is a potential oncogene in anaplastic thyroid carcinoma. Nucera, C., Eeckhoute, J., Finn, S., Carroll, J.S., Ligon, A.H., Priolo, C., Fadda, G., Toner, M., Sheils, O., Attard, M., Pontecorvi, A., Nose, V., Loda, M., Brown, M. Clin. Cancer Res. (2009) [Pubmed]
  5. GATA-3 Maintains the Differentiation of the Luminal Cell Fate in the Mammary Gland. Kouros-Mehr, H., Slorach, E.M., Sternlicht, M.D., Werb, Z. Cell (2006) [Pubmed]
  6. From the Cover: Location analysis of estrogen receptor alpha target promoters reveals that FOXA1 defines a domain of the estrogen response. Laganière, J., Deblois, G., Lefebvre, C., Bataille, A.R., Robert, F., Giguère, V. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  7. Insulin regulates the activity of forkhead transcription factor Hnf-3beta/Foxa-2 by Akt-mediated phosphorylation and nuclear/cytosolic localization. Wolfrum, C., Besser, D., Luca, E., Stoffel, M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  8. FOXA1 as a therapeutic target for breast cancer. Nakshatri, H., Badve, S. Expert Opin. Ther. Targets (2007) [Pubmed]
  9. Expression and role of Foxa proteins in prostate cancer. Mirosevich, J., Gao, N., Gupta, A., Shappell, S.B., Jove, R., Matusik, R.J. Prostate (2006) [Pubmed]
  10. FOXA1 expression in breast cancer--correlation with luminal subtype A and survival. Badve, S., Turbin, D., Thorat, M.A., Morimiya, A., Nielsen, T.O., Perou, C.M., Dunn, S., Huntsman, D.G., Nakshatri, H. Clin. Cancer Res. (2007) [Pubmed]
  11. BRCA1 and FOXA1 proteins coregulate the expression of the cell cycle-dependent kinase inhibitor p27(Kip1). Williamson, E.A., Wolf, I., O'Kelly, J., Bose, S., Tanosaki, S., Koeffler, H.P. Oncogene (2006) [Pubmed]
  12. The Foxa family of transcription factors in development and metabolism. Friedman, J.R., Kaestner, K.H. Cell. Mol. Life Sci. (2006) [Pubmed]
  13. Expression of Foxa transcription factors in the developing and adult murine prostate. Mirosevich, J., Gao, N., Matusik, R.J. Prostate (2005) [Pubmed]
  14. Specific Interactions of the Wing Domains of FOXA1 Transcription Factor with DNA. Cirillo, L.A., Zaret, K.S. J. Mol. Biol. (2007) [Pubmed]
  15. Proximal promoter of the surfactant protein D gene: regulatory roles of AP-1, forkhead box, and GT box binding proteins. He, Y., Crouch, E.C., Rust, K., Spaite, E., Brody, S.L. J. Biol. Chem. (2000) [Pubmed]
  16. Hepatocyte nuclear factor 3 relieves chromatin-mediated repression of the alpha-fetoprotein gene. Crowe, A.J., Sang, L., Li, K.K., Lee, K.C., Spear, B.T., Barton, M.C. J. Biol. Chem. (1999) [Pubmed]
  17. Modulation of liver-specific transcription by interactions between hepatocyte nuclear factor 3 and nuclear factor 1 binding DNA in close apposition. Jackson, D.A., Rowader, K.E., Stevens, K., Jiang, C., Milos, P., Zaret, K.S. Mol. Cell. Biol. (1993) [Pubmed]
WikiGenes - Universities