Biology:FOXA1

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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 FOXA1 gene.[1][2][3]

Function

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 cancer

Mutations in this gene have been recurrently seen in instances of prostate cancer.[8]

Expression of FOXA1 correlates with two EMT markers, namely Twist1 and E-cadherin in breast cancer.[9]

References

  1. 1.0 1.1 "Entrez Gene: forkhead box A1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3169. 
  2. "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. June 1996. doi:10.1016/0167-4781(96)00058-9. PMID 8652662. 
  3. "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. February 1997. doi:10.1006/geno.1996.4477. PMID 9119385. 
  4. "Differential oestrogen receptor binding is associated with clinical outcome in breast cancer". Nature 481 (7381): 389–393. January 2012. doi:10.1038/nature10730. PMID 22217937. Bibcode2012Natur.481..389R. 
  5. "GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland". Cell 127 (5): 1041–1055. December 2006. doi:10.1016/j.cell.2006.09.048. PMID 17129787. 
  6. "Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours". Breast Cancer Research 11 (3): R40. 2009. doi:10.1186/bcr2327. PMID 19549328. 
  7. "Gene expression meta-analysis supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB family". BMC Medical Genomics 2: 59. September 2009. doi:10.1186/1755-8794-2-59. PMID 19747394. 
  8. "Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer". Nature Genetics 44 (6): 685–689. May 2012. doi:10.1038/ng.2279. PMID 22610119. 
  9. "Association of FOXA1 and EMT markers (Twist1 and E-cadherin) in breast cancer". Molecular Biology Reports 46 (3): 3247–3255. June 2019. doi:10.1007/s11033-019-04784-w. PMID 30941644. 

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.