Snail family transcription factors are implicated in thyroid carcinogenesis.
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.
Hardy
Robert G
RG
Tissue Injury and Repair Group, Centre for Regenerative Medicine, University of Edinburgh, Division of Clinical and Surgical Sciences, Room FU501, Chancellors Bldg, 49 Little France Crescent, Edinburgh EH16 4SB, UK. r.hardy@ed.ac.uk
Vicente-Dueñas
Carolina
C
González-Herrero
Ines
I
Anderson
Catriona
C
Flores
Teresa
T
Hughes
Sharon
S
Tselepis
Chris
C
Ross
James A
JA
Sánchez-García
Isidro
I
D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D000071250:Snail Family Transcription Factors; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C000604407:SNAI1 protein, human; C000604408:SNAI2 protein, human; C000604429:Snai1 protein, mouse; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors