Expression Of TGFβ1 And Related Cell Cycle Regulators In Bladder Transitional Cell Carcinoma And Their Regulation On Cell Proliferation

Recent years lots of studies have been done on the role of TGF B 1 in neoplasms including bladder transitional cell carcinoma. But the results don't agree each other. The manifold biological activities of TGF B 1 turn essentially around three poles: (1)regulation of cell proliferation differentiation and apoptosis (2) enhancement of extracellular matrix deposition and stimulation of tumor angiogenesis (3)suppression of immunological function. TGF B 1 is a potent growth inhibitor in epithelial tissues. Studies suggest the inhibition is achieved by inducing the expression of some cell cycle regulators. No studies on TGF B 1 and cell cycle regulators in TCC have been reported to date. P21WAF1/CIP1 and Cyclin D1 both play important roles in cell cycle. Ki-67 can determine the proliferative potential of tumor cells. In present study, in order to investigate the role of TGF (3 1 on cell cycle in bladder TCC, we detected the expression of TGF B 1, p21wAF1/CIP1,Cyclin D1 and Ki-67 in specimens of patients withbladder transitional cell carcinoma.The expression of TGF B 1 , P21WAF1/CIP1 , Cyclin D1 and Ki-67 was examined in 50 cases of bladder transitional cell carcinoma and 10 normal bladder mucosas by means of immunohistochemical SP technique. The results of immunohistochemical staining were categorized into three grades including (-) (+) and (++). Thecorrelations between the expression results and tumor pathological grades, clinical stages, number of lessions were studied.The positive rate of TGF B 1 was significantly higher in TCC patients(58%) than in the normal mucosas(20%). Furthermore, its expression decreased with the advance of tumor grade and tumor stage. The primary tumor group had a higher level expression of TGF B 1 than recurrent tumor group. The positive rate of P21 in TCC group was 54%, significantly higher than in normal mucosas group(10%). And its expression had negative correlation with tumor grade and tumor stage. Moreover, primary tumors expressed higher level of P21 than recurrent tumors. Cyclin D1 expression was not detected in normal mucosas, while the positive rate in TCC was 58%. And its expression level elevated with the advance of tumor grade and tumor stage, but there was not statistical significance. The primary tumor group had a higher expression level of P21 than recurrent tumor group. Ki-67LI in BTCC was significantly higher than normal mucosas and Ki-67 expression positively correlated with both increased grade and stage. There were higher expression levels of Ki-67 in recurrent tumors and multiple tumors than in primary ones and solitary ones. There was positive correlation both between Cyclin D1 and Ki-67 and between TGFB 1 and P21. Otherwise, TGFB 1 and Ki-67 , P21 and Ki-67 had negative correlation. Moreover there was no correlationbetween TGF B1 and Cyclin D1 or between P21 and Cyclin D1.These results suggest that as a potent tumor growth inhibitor, TGF B 1 expression increases in early stage. At the same time P2 1 expression goes up induced by TGF B 1 . Then high expression level of P21 can inhibit the function of Cyclin D1-CDK4/6 complexes which will accelerate cell cycle and promote tumor progression. So tumor growth will be in part inhibited. In late stage, TGF B 1 expression decreases and induction of P21 also reduces. So Cyclin Dl will accelerate cell cycle more strongly and result in progression of tumor. Ki-67LI will be higher.