The Expression Of Bcl-2, CyclinD1, P27^kip1 In Renal Cell Carcinoma And Relativity Investigation

Background and ObjectivesRenal carcinoma, which has the other name is renal cell carcinoma, is the most common malignant renal cortical tumor. Its incidence is nearly similar to bladder cancer and ranks the second in urologic tumor. But the incidence rate of renal carcinoma is showing an ascending tendency in recent year. Because its morbidity is delitescence; it has metastasized to another area in the prophase and the early symptoms are often untypical, when typical clinical symptoms are showing, a lots of patients have been developing metaphase or advanced stage. Nowadays, the diagnosis of renal carcinoma depends on imageology combining with the surgeon experience. In particular, it is difficult to discover renal cell carcinoma in the early stage and it is difficult to guide the therapy in the early stage. As a result, using molecular biology to diagnose RCC have being searched by scholar overworld.Codogenic product of apoptosis inhibiting gene bcl-2 is situated in membrane formation, especially, mitochondrial membrane. Bcl-2 can inhibit cell apoptosis by cutting-out Ca2+ release from endoplasmic reticulum, inhibition of caspases and cutting-out IP3 signal transduction path and so on. In normal cell cycle, cyclinDl-cdk4 (cyclin dependent kniase, CDK4) compound enable starte synthesis of DNA, and cell cycle is enhanced from G1 to S by the compound. It help cell to do propagation. CyclinDl and bcl-2 are positive regulation factor of cell propagation. P27kipl is an inhibitor of cell cycle dependant kinase. It can suppress cells cycle by inhibition of activation of cyclinE-CDK2 and cyclinD-CDK4 compound. P27kipl educe down-regulation. Immunohistochemisty certifyed that cyclinDl and bcl-2 were higher expression. P27kipl was lower expression in gastric carcinoma, colon cancer, breast carcinoma and so on. Nowaday, it has been few reported that using RT-PCR detected expression of bcl-2, cyclinD1, p27kipl in renal cell carcinoma in domestic. And there were not report of relativity of bcl-2, cyclinD1, p27kipl.We have investigated expression and mechanism of bcl-2, cyclinDl and p27kipl in renal cell carcinoma (RCC) and explored their clinical value of diagnosis, judgement prognosis and guiding therapy for RCC. And we have analyzed the relativity of bcl-2, cyclinDl and p27kipl.Materials and Methods1.42 cases RCC were assembled in The Second Affiliated Hospital of Zhengzhou University, Henan Province Tumor Hospital and Henan Province People Hospital from Dec,2008 to Jun,2009, including 27 males and 15 females,the ages ranged from 30 to 82 years old (mean:57 years). Histopathologic types as following: 33 RCC cases were clear cell carcinoma and 9 RCC cases were non-clear cell carcinoma. Clinical stages:Ⅰ10 casesⅡ13 casesⅢ12 casesⅣ7 cases.10 cases normal renal tissues, as control groups, were obtained from pations of renal trauma, double kidney, moderate ureter carcinoma and hypo-ureter carcinoma; and these cases tissues were certified by histopathology. About 500 mg fresh kidney tissue specimens were put into the RNAse-Free EP tubes immediately after operation cutting and soaked in RNAse-Blocker liquid for 24 hours, then stored in-80℃refrigerator.2. Bcl-2, cyclinDl, p27kipl mRNA in the renal cell carcinoma tissues and normal renal tissues had been studied by RT-PCR, and the relationship of had been analyzed.3. All dates were statistically analyzed by SPSS 11.0 software. a=0.05 was considered the significant level of two-sided test.Results1. The median expressional level of bcl-2 mRNA (0.56) in 42 RCC tissues significantly higher than that level(0.13) in normal tissues, (P< 0.05). The median expressional level of cyclinD1 mRNA (0.56) in the RCC tissues significantly higher than that level(0.15) in normal tissues, (P< 0.05), and the median expressional level of p27kiplmRNA was 0.46,which significantly lower than that level(0.86)in normal renal tissues (P< 0.05). The expression of bcl-2 mRNA in clinical stageⅠ+Ⅱhigher than the expression in stageⅢ+IV(P< 0.05). The expression of cyclinD1 mRNA in clinical stageⅠ+Ⅱlower than the expression in stageⅢ+Ⅳ(P< 0.05).But p27kipl mRNA was less and less. The bcl-2 expressional level in clear cell RCC and non-clear cell RCC were 0.58±0.19 and 0.39±0.18,t=2.74, (P< 0.05). cyclinD1mRNA expression level in clear cell RCC and non-clear cell RCC were 0.66±0.08 and 0.55±0.08, t=3.50, (P< 0.05). The p27kipl mRNA expression in non-clear cell RCC and clear cell RCC were 0.49±0.2 and 0.45±0.16,t=0.50, (P> 0.05), and they are not difference.2. Partial correlation analysis:the coefficient of p27kipl and cyclinD1 were-0.57, (P<0.05). The coefficient of p27kipl and bcl-2 were 0.44, (P< 0.05). The coefficient of cyclinD1 and bcl-2 were-0.06 (P> 0.05).Conclusions1. The expression of bcl-2 and cyclinD1 in renal cell carcinoma tissues were significantly higher than normal tissues, and their expression in clear cell RCC were significantly higher than non-clear cell RCC. The expression of p27kipl in renal cell carcinoma tissues were significantly lower than normal tissues, and the expression of p27kipl in clear cell RCC and non-clear cell RCC were not difference.2. Detection the expression of bcl-2, cyclinDl, p27kipl mRNA can help to diagnose and evaluate RCC.3. It was negatively correlation between p27kipl and cyclinDl. But it was positive correlation between p27kipl and bcl-2; however, between cyclinD1 and bcl-2 had nothing correlativity.