摘要
背景与目的:近一半的胰腺癌存在DPC4/Smad4失活,使肿瘤细胞增殖的抑制作用丧失;p21waf1是Smad4调控的下游靶基因,而DPC4和p16基因在胰腺癌的发生中可能有协同作用。本研究拟通过研究DPC4/Smad4、p21wafI、p16蛋白在人胰腺癌中的表达情况,探讨三者之间的关系及它们在胰腺癌中的可能作用机制。方法:用免疫组化技术检测56例石蜡包埋人胰腺癌组织Smad4、p21wafI、p16的蛋白表达情况;用原位杂交、免疫组化技术、Westernblot检测5株人胰腺腺癌细胞系中DPC4/Smad4的mRNA和蛋白表达情况。结果:石蜡包埋人胰腺癌组织免疫组化显示Smad4、p21wafI和p16阳性率分别为58.93%、48.21%和42.86%,对应癌旁非癌胰腺组织阳性率分别为89.29%、87.5%和76.79%;P3、P4、P7人胰腺腺癌细胞系DPC4/Smad4的原位杂交、免疫组化及Westernblot均为阳性,而P1、P2均为阴性。统计学分析显示胰腺癌及癌旁非癌胰腺之间3种蛋白表达均有显著性差异(P<0.05),胰腺癌中Smad4与p21wafI表达之间有一定相关性(P<0.05),Smad4与p16表达之间有一定相关性(P<0.05),但p21wafI与p16表达之间无显著相关(P>0.05)。结论:胰腺癌与正常胰腺相比,Smad4、p21wafI、p16蛋白表达明显下降,其改变在胰腺癌的发生发展中可能起重要作用。
Background &Objective:DPC4/Smad4inactivation was detected in almost half of the pancreatic carcinomas result in the loss of inhi bition of the tumor cell proliferati on.p21waf1is the downstream target gene of Smad4while DPC4and p16may synergis tically play a role in the developmen t of pancreatic carcinoma.By studying the expressions of DPC4/Smad4,p21wafI,and p16.This study was designed to e xplore the mutual relationship amon g them and the possible mechanism in human pancreatic carcinoma.Methods :Immunohistochemistry was used to detect the expression of Smad4,p21wafI,and p16in fifty-six samples of para ffin embedded human pancreatic cancer tissue,and in situ hybridization,immunohistochemis try,Western blotting technique were used to detect the expression of DPC4/Smad4in five human pancreatic adenocarcinoma cell lines.Results:The positive rate of Smad4,p21 wafI ,and p16in paraffin embedded human pancreatic cancer tissue was 58.93%,48.21%,and 42.86%,respectively,whereas the positive rate of these proteins in matched normal tissue was 89.29%,87.5%,and 76.79%respectively.Thr ee out of five pancreatic adenocarcinoma cell lin es(P3,P4,and P7)were positive for DPC4/Smad4with in situ hybridization,immunohistochemistry and Western b lotting,while the other two lines were all negative.There is statistically significant difference between cancer and norma l tissue(P<0.05).In pancreatic adenocarcinomas,the ex pression of Smad4was related to that of p21wafI(P<0.05),and so was the expression of Smad4to that of p16(P<0.05).But no correlation was found between p21wafIand p16(P>0.05).Conclusion:The expression of Smad4,p21 wafI,and p16significantly decreased in pancreatic cancer compared with normal tissue.The decreased expression of the protein s may play an important role in the dev elopment of pancreatic cancer.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2002年第2期132-137,共6页
Chinese Journal of Cancer
基金
国家杰出青年基金项目(No.39625012)
国家教委跨世纪优秀人才计划基金项目
