FOXA1 is a potential oncogene in anaplastic thyroid carcinoma.

TitleFOXA1 is a potential oncogene in anaplastic thyroid carcinoma.
Publication TypeJournal Article
Year of Publication2009
AuthorsNucera C, Eeckhoute J, Finn S, Carroll JS, Ligon AH, Priolo C, Fadda G, Toner M, Sheils O, Attard M, Pontecorvi A, Nose V, Loda M, Brown M
JournalClin Cancer Res
Volume15
Issue11
Pagination3680-9
Date Published2009 Jun 01
ISSN1078-0432
KeywordsAdult, Aged, Aged, 80 and over, Apoptosis, Blotting, Western, Carcinoma, Cell Proliferation, Cohort Studies, Cyclin-Dependent Kinase Inhibitor p27, Female, Flow Cytometry, Gene Dosage, Gene Expression Regulation, Neoplastic, Hepatocyte Nuclear Factor 3-alpha, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Intracellular Signaling Peptides and Proteins, Male, Middle Aged, Oncogene Proteins, RNA, Small Interfering, Thyroid Neoplasms, Tissue Array Analysis, Transfection
Abstract

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.

DOI10.1158/1078-0432.CCR-08-3155
Alternate JournalClin Cancer Res
PubMed ID19470727
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