FOXA1

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Forkhead box A1
Identifiers
Symbols FOXA1 ; HNF3A; TCF3A
External IDs OMIM602294 MGI1347472 HomoloGene3307 GeneCards: FOXA1 Gene
Orthologs
Species Human Mouse
Entrez 3169 15375
Ensembl ENSG00000129514 ENSMUSG00000035451
UniProt P55317 P35582
RefSeq (mRNA) NM_004496 NM_008259
RefSeq (protein) NP_004487 NP_032285
Location (UCSC) Chr 14:
38.06 – 38.07 Mb
Chr 12:
57.54 – 57.55 Mb
PubMed search [1] [2]

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[edit]

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[edit]

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[edit]

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

References[edit]

  1. ^ a b "Entrez Gene: forkhead box A1". 
  2. ^ 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. PMID 8652662. 
  3. ^ 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. PMID 9119385. 
  4. ^ Ross-Innes, Caryn S.; Stark, Rory; Teschendorff, Andrew E.; Holmes, Kelly A.; Ali, H. Raza; Dunning, Mark J.; Brown, Gordon D.; Gojis, Ondrej; Ellis, Ian O.; Green, Andrew R.; Ali, Simak; Chin, Suet-Feung; Palmieri, Carlo; Caldas, Carlos; Carroll, Jason S. (4 January 2012). "Differential oestrogen receptor binding is associated with clinical outcome in breast cancer". Nature. doi:10.1038/nature10730. PMC 3272464. 
  5. ^ Kouros-Mehr H, Slorach EM, Sternlicht MD, Werb Z (December 2006). "GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland". Cell 127 (5): 1041–55. doi:10.1016/j.cell.2006.09.048. PMC 2646406. PMID 17129787. 
  6. ^ Albergaria A, Paredes J, Sousa B, Milanezi F, Carneiro V, Bastos J, Costa S, Vieira D, Lopes N, Lam EW, Lunet N, Schmitt F (2009). "Expression of FOXA1 and GATA-3 in breast cancer: The prognostic significance in hormone receptor-negative tumours". Breast Cancer Research 11 (3): R40. doi:10.1186/bcr2327. PMC 2716509. PMID 19549328.  edit
  7. ^ Sanga S, Broom BM, Cristini V, Edgerton ME (2009). "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. doi:10.1186/1755-8794-2-59. PMC 2753593. PMID 19747394.  edit
  8. ^ 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. PMC 3673022. PMID 22610119. 

Further reading[edit]

External links[edit]

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