title: Expression of Snail and Slug in renal cell carcinoma: E-cadherin repressor Snail is associated with cancer invasion and prognosis.
abstract: The Snail family transcription factors have been proposed as important mediators of epithelial-mesenchymal transition because of their role in down-regulation of E-cadherin and up-regulation of matrix metalloproteinases (MMPs). The present study was undertaken to investigate the expression of Snail, Slug and their associations with cancer invasion and prognosis in renal cell carcinomas (RCCs). Ninety-seven primary RCCs were analyzed for the protein expression of Snail, Slug, MMP2 and MMP9 by immunohistochemistry. Snail protein expression level was positively correlated with pathological tumor stage, histological grade and the presence of sarcomatoid carcinoma. On the contrary, Slug protein expression level was negatively correlated with pathological tumor stage, suggesting that Slug was down-regulated in advanced RCCs. Because Snail was positively associated with malignant potential of RCCs, involvement of Snail in the invasiveness of an RCC cell line 786-O was examined in the Matrigel invasion assay by down-regulating the gene expression with small interfering RNA (siRNA). Targeting the Snail, not Slug, expression in 786-O cells with siRNA caused down-regulation of the gene expression of Snail, vimentin, MMP2 and MMP9, but up-regulated the E-cadherin. Invasion of the cells through Matrigel in vitro was inhibited under this condition. Furthermore, expression levels of MMP2 and MMP9 were positively correlated with pathological tumor stage and the presence of sarcomatoid carcinoma. Statistical analysis indicated that elevated Snail, MMP2 and MMP9 protein expression are significantly worse predictors of disease-free and disease-specific survival of the patients with RCC. In conclusion, these data suggest that Snail has an important role in invasion and metastasis, and that silencing the gene may be a potential therapeutic target in RCCs.
authors.affiliation: Division of Diagnostic Pathology, Keio University Hospital, Tokyo, Japan. mikami@a7.keio.jp
authors.forename: Shuji
authors.initials: S
authors.lastname: Mikami
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Katsube
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Oya
authors.forename: Masaru
authors.initials: M
authors.lastname: Ishida
authors.forename: Takeo
authors.initials: T
authors.lastname: Kosaka
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Mizuno
authors.forename: Makio
authors.initials: M
authors.lastname: Mukai
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Okada
mesh_terms: D015820:Cadherins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D018390:Gene Targeting; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015820:Cadherins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9