Abstract
BackgroundSlug, 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.MethodsWe 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).ResultsExpression 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).ConclusionsThese 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.
Highlights
Slug, Snail, and Twist are transcription factors that regulate the expression of tumor suppressors such as E-cadherin
Expression of Snail, Slug, Twist and E-cadherin in human bladder cancer cell lines The expression of Snail, Slug, Twist and E-cadherin was analyzed at the mRNA and protein level by semiquantitative RT-PCR(Fig. 1A) and western blot (Fig. 1B) in the human bladder cancer cell lines T24, HTB-3, HTB-1, HTB-2 and HTB-9
Twist mRNA and protein was detected in HTB-1 and T24 cells, no appearant Twist mRNA and protein expression was found in other 3 cell lines
Summary
Snail, and Twist are transcription factors that regulate the expression of tumor suppressors such as E-cadherin. The transcriptional factors Snail and Slug (zinc finger proteins) have been described to be direct repressors of E-cadherin [6,7,8,9,10,11] in vitro and in vivo through an interaction of their COOH-terminal region with a 5′CACCTG-3′ sequence in the E-cadherin promoter [12]. Both have been suggested to be involved in the acquisition of resistance to apoptosis, thereby promoting tumor survival. Gender - number of patients Male 87 (72) Female 33 (28)
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