Expression of transcription factors snail, slug, and twist in human bladder carcinoma

Abstract

BACKGROUND: Slug, snail, and twist are transcription factors that regulate the expression of tumor suppressors such as E-cadherin. In this study, we aimed to examine the expression of these transcription factors in human bladder carcinoma. METHODS: We first investigated expression of slug, snail, twist and E-cadherin in five bladder Carcinoma cell lines by reverse transcription-polymerase chain reaction and western blotting. Furthermore, we investigated slug, snail, and twist and E-cadherin expression by immunohistochemistry with bladder carcinoma (tumor, n = 120; background, n = 42). RESULTS: Expression of slug mRNA and protein was detected in all cell lines, twist was clearly expressed in two out of five bladder carcinoma cell lines, snail was not expressed, and E-cadherin was detected in 3 cell lines. 44.2% (53/120) of human bladder carcinoma tissues and 38% (16/42) background tissue showed an expression of twist; 62.5% (75/120) of human bladder carcinoma tissues and 40% (17/42) background tissue showed an expression of slug, 15.8% (19/120) of human bladder carcinoma tissues and 76% (32/42) background tissue showed an expression of snail, and 25.8% (31/120) cases were negative for E-cadherin expression in carcinoma tissues. Expression of slug and twist shows increased levels in tumors, whereas snail seems reduced. Statistically significant correlations were found between twist, slug, and E-cadherin expression. Immunohistochemistry analysis showed that twist was elevated with increasing tumor stage (P = 0.001), the grade (P < 0.001), the progression (P = 0.035). Slug was elevated and snail was reduced with increasing nodal involvement (tumor-node-metastasis status) (P = 0.004, P = 0.01). E-cadherin was reduced in expression corresponding with tumor grade (P < 0.01). Positive twist, slug and E-cadherin expression clearly predicted poorer PFS (P = 0.042, P = 0.014, P = 0.001). In the multivariate analysis, only snail and E-cadherin expression were independent prognostic factors for OS (P = 0.002, P < 0.001). CONCLUSIONS: These data demonstrate that twist, snail and slug have inappropriate expression in bladder carcinoma and that this may play a part in the progression of human bladder carcinoma.