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(American Journal of Pathology. 2007;171:1037-1046.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.061211

Snail Family Transcription Factors Are Implicated in Thyroid Carcinogenesis

Robert G. Hardy*, Carolina Vicente-Dueñas{dagger}, Ines González-Herrero{dagger}, Catriona Anderson{ddagger}, Teresa Flores§, Sharon Hughes, Chris Tselepis, James A. Ross* and Isidro Sánchez-García{dagger}

From the Tissue Injury and Repair Group,* Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom; the Department of Pathology,{ddagger} Royal Infirmary of Edinburgh, Edinburgh, United Kingdom; the Cancer Research United Kingdom Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom; and the Experimental Therapeutics and Translational Oncology Program,{dagger} Instituto de Biología Molecular y Celular del Cáncer, and the Pathology Department,§ Consejo Superior de Investigaciones Cientificas/Universidad de Salamanca, Salamanca, Spain

E-Cadherin (CDH1) expression is reduced in thyroid carcinomas by primarily unknown mechanisms. In several tissues, SNAIL (SNAI1) and SLUG (SNAI2) induce epithelial-mesenchymal transition by altering target gene transcription, including CDH1 repression, but these transcription factors have not been studied in thyroid carcinoma. Recently, our group has provided direct evidence that ectopic SNAI1 expression induces epithelial and mesenchymal mouse tumors. SNAI1, SNAI2, and CDH1 expression were analyzed in thyroid-derived cell lines and samples of human follicular and papillary thyroid carcinoma by reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry. The effect of SNAI1 expression on CDH1 transcription was analyzed by reverse transcriptase-polymerase chain reaction and Western blotting in ori-3 cells. Thyroid carcinoma development was analyzed in CombitTA-Snail mice, in which SNAI1 levels are up-regulated. SNAI1 and SNAI2 were not expressed in cells derived from normal thyroid tissue, or in normal human thyroid samples, but were highly expressed in cell lines derived from thyroid carcinomas, in human thyroid carcinoma samples, and their metastases. SNAI1 expression in ori-3 cells repressed CDH1 transcription. Combi-TA mice developed papillary thyroid carcinomas, the incidence of which was increased by concomitant radiotherapy. In conclusion, SNAI1 and SNAI2 are ectopically expressed in thyroid carcinomas, and aberrant expression in mice is associated with papillary carcinoma development.




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M. Herfs, P. Hubert, N. Kholod, J. H. Caberg, C. Gilles, G. Berx, P. Savagner, J. Boniver, and P. Delvenne
Transforming Growth Factor-{beta}1-Mediated Slug and Snail Transcription Factor Up-Regulation Reduces the Density of Langerhans Cells in Epithelial Metaplasia by Affecting E-Cadherin Expression
Am. J. Pathol., May 1, 2008; 172(5): 1391 - 1402.
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