抑癌基因PTEN/MMAC1/TEP1在肾癌组织中的表达及其与细胞增殖和凋亡的关系

Correlation between the PTEN /MMAC1/TEP1 Expression and Cell Proliferation and Apoptosis in Human Renal Cell Carcinoma (RCC)

背景与目的:PTEN/MMAC1/TEP1是近来新发现的具有磷酸酯酶活性的抑癌基因,有研究证实PTEN在人类多种肿瘤中存在丢失或突变,与肿瘤的发生、发展密切相关,但在肾癌中研究较少。本研究拟探讨肾细胞癌(renalcellcarcinoma,RCC)中抑癌基因PTEN的蛋白表达及其与肾癌生物学行为的关系。方法:收集44例手术后并经病理学检查证实的RCC组织、15例癌旁非癌肾组织及10例非瘤正常肾组织,采用免疫组化SP法进行PTEN蛋白检测,按PTEN蛋白阴、阳性各选15例RCC组织和10例正常肾组织,用流式细胞仪检测细胞的增殖指数和凋亡率,从而分析PTEN蛋白与肾细胞增殖和凋亡的关系。结果:PTEN蛋白在肾组织中表达主要位于胞浆,RCC组织中PTEN阳性表达率为36.36%,显著低于癌旁非癌肾组织(73.33%)及正常肾组织(100%)(P<0.01),在不同组织类型中无统计学差异(P>0.05)。PTEN蛋白在Ⅰ、Ⅱ期RCC组织中表达显著高于Ⅲ、Ⅳ期RCC组织(P<0.05),PTEN蛋白阳性RCC细胞的增殖指数为(5.6±0.8)%,显著低于PTEN蛋白阴性者的(15.6±1.6)%(P<0.01),而PTEN蛋白阳性者的细胞凋亡率为(6.5±1.9)%,显著高于PTEN蛋白阴性者的(2.8±1.6)%(P<0.01)。结论:PTEN蛋白在RCC组织中的阳性表达明显下降,其抑癌作用机制可能是诱导细胞周期阻滞在G1期和增加细胞凋亡率。

BACKGROUND &OBJECTIVE:PTEN is a tumor suppressor g ene with phosphatase activity.It had been proved the aberrant expressi on and mutation of PTEN in diverse types of human cancer;PTEN is closely associa ted with occurrence and development of m alig nant tumor.This study was conducted to investig ate the expression of PTE N /MMAC1/TEP1g ene product in human renal cell carcinoma (RCC)and the correlation between the expr ession of PTEN and the biolog ical behaviors of RCC.METHODS :The PTEN protein of 44cases of RCC tissues confirmed by patholog y after operation,15cases of adjacent normal renal tissues ,and 10cases of non-tumor normal renal tissues were assessed using immunohistochemical technique(SP).Fifteen RCC tissues and10normal renal tissues selected res pectively from the renal tissues who se PTEN protein expression were positive as well as those from the neg ative were made to be the cell suspension ming led with p araffin.The proliferative index an d the apoptosis incidence were examined b y flow cytometry and the correlation between PTEN protein and the prolife ration and apoptosis were analyzed.RESULTS :The expression of PTEN protein was mo stly located in the renal cell plasma.The positive incidence of expression PTEN protein in RCC was 36.3%which was prominently lower than tho se in the adjacent normal tissues (77.3%)and the normal tissues (100.00%)(P<0.01).There was no sig nificant difference between the different so rts of tissues (P>0.05).The expression of PTEN in stag e Ⅰ,Ⅱis much hig her than that in stag e Ⅲ,Ⅳ(P<0.05).The proliferative index of RCC whose exp ression of PTEN protein was positive(5.6±0.8)%was sig nificantly lower than that o f neg ative(15.6±1.6)%(P<0.01).While the apoptosis incidence was (6.5±1.9)%,which was much hig her than that of RCC whose expression was (2.9±1.6)%(P<0.01).CONCLUSION:The positive expression incidence o f PTEN protein sig nificantly decreases in RCC tissues.PTEN protein suppresses carcinoma by inducing the cell cycle to be blocked up in G 1 phase and increasing the apoptosis i ncidence.The assessment of the expression PTEN protein is one of the important indexes of the development and prog nosis of RCC.