FOXA1 Is a Potential Oncogene in Anaplastic Thyroid Carcinoma
- Carmelo Nucera1,
- Jerome Eeckhoute1,
- Stephen Finn2,
- Jason S. Carroll3,
- Azra H. Ligon2,10,
- Carmen Priolo4,
- Guido Fadda5,
- Mary Toner6,
- Orla Sheils7,
- Marco Attard8,
- Alfredo Pontecorvi9,
- Vânia Nose10,
- Massimo Loda2,4,10 and
- Myles Brown1,11
- Authors' Affiliations:1Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; 2Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; 3Cancer Research UK, Cambridge Research Institute, Cambridge, United Kingdom; 4Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston; 5Division of Anatomic Pathology and Histology, Catholic University School of Medicine “A. Gemelli,” Rome, Italy; 6Oral Pathology, Dublin Dental School and Hospital, University of Dublin Trinity College, Lincoln Place, Dublin, Ireland; 7Department of Pathology, University of Dublin Trinity College, Trinity Centre for Health Sciences, St. James's Hospital, Dublin, Ireland; 8Endocrinology Unit, Hospital “V. Cervello” of Palermo, Palermo, Italy; 9Endocrinology Unit, Catholic University School of Medicine “A. Gemelli,” Rome, Italy; 10Department of Pathology, Brigham and Women's Hospital, Harvard Medical School; and 11Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- Requests for reprints:
Myles Brown, Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, D730, Boston, MA 02115. Phone: 617-632-3948; Fax: 617-582-8501; E-mail: myles_brown{at}dfci.harvard.edu.
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 G1 growth arrest and reduction of cell proliferation. Moreover, we observe a potential link between FOXA1 and the cell cycle machinery by identifying p27kip1 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.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).
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- Accepted March 3, 2009.
- Received December 4, 2008.
- Revision received February 10, 2009.
