Document Detail


FOXA1 is a potential oncogene in anaplastic thyroid carcinoma.
MedLine Citation:
PMID:  19470727     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: FOXA1 is a mammalian endodermal transcription factor belonging to the human forkhead box gene family that plays a role in certain tumor types. Here, we investigated the potential role of FOXA1 in human thyroid carcinomas. EXPERIMENTAL DESIGN: We examined the level of FOXA1 expression and gene copy number by immunohistochemistry and fluorescence in situ hybridization, respectively, in a cohort of benign and malignant thyroid tumors. In addition, we examined the role of FOXA1 in the proliferation of an undifferentiated thyroid carcinoma cell line by short hairpin RNA-mediated silencing. RESULTS: We show that FOXA1 is overexpressed in human anaplastic thyroid carcinomas (ATC). In addition, we identify FOXA1 DNA copy number gain within the 14q21.1 locus in both an ATC cell line and human ATC cases. Silencing of FOXA1 in an ATC cell line causes G(1) growth arrest and reduction of cell proliferation. Moreover, we observe a potential link between FOXA1 and the cell cycle machinery by identifying p27(kip1) up-regulation on FOXA1 silencing. CONCLUSIONS: FOXA1 is overexpressed in aggressive thyroid cancers and involved in cell cycle progression in an ATC cell line. Therefore, FOXA1 may be an important oncogene in thyroid tumorigenesis and a potential new therapeutic target for the treatment of anaplastic thyroid cancers.
Authors:
Carmelo Nucera; Jerome Eeckhoute; Stephen Finn; Jason S Carroll; Azra H Ligon; Carmen Priolo; Guido Fadda; Mary Toner; Orla Sheils; Marco Attard; Alfredo Pontecorvi; Vânia Nose; Massimo Loda; Myles Brown
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Publication Detail:
Type:  Journal Article     Date:  2009-05-26
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  15     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-02     Completed Date:  2009-07-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3680-9     Citation Subset:  IM    
Affiliation:
Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Apoptosis
Blotting, Western
Carcinoma / genetics,  metabolism,  pathology*
Cell Proliferation
Cohort Studies
Female
Flow Cytometry
Gene Dosage
Gene Expression Regulation, Neoplastic
Hepatocyte Nuclear Factor 3-alpha / genetics,  metabolism*
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Intracellular Signaling Peptides and Proteins / genetics,  metabolism
Male
Middle Aged
Oncogene Proteins / genetics,  metabolism*
RNA, Small Interfering / genetics
Thyroid Neoplasms / genetics,  metabolism,  pathology*
Tissue Array Analysis
Transfection
Chemical
Reg. No./Substance:
0/CDKN1B protein, human; 0/FOXA1 protein, human; 0/Hepatocyte Nuclear Factor 3-alpha; 0/Intracellular Signaling Peptides and Proteins; 0/Oncogene Proteins; 0/RNA, Small Interfering

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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