摘要
目的:探讨mdm2,Rb基因表达与胃癌发生及胃癌生物学行为的关系.方法:采用免疫组织化学技术(S-P法)检测18例正常胃黏膜、26例异型增生胃黏膜、18例早期胃癌、38例进展期胃癌患者组织中的MDM2,Rb基因蛋白的表达情况,并与临床病理特征相比较.在此基础上,我们通过RNAi技术特异性降低mdm2的表达水平,观察细胞周期的变化,探讨了mdm2作用的分子机制.结果:MDM2蛋白在正常胃黏膜、I型及II型增生胃黏膜、早期胃癌及进展期胃癌组织中的阳性表达率分别为33.3%,40.0%,43.8%,55.6%,57.9%.Rb蛋白的阳性表达率分别为94.4%,100.0%,81.3%,55.6%,63.2%.随着胃黏膜病变的进展,MDM2表达率逐渐增高,在进展期胃癌中达到高峰,但各组间相比差异无统计学意义(P>0.05).Rb的表达呈相反的趋势,在I型增生中表达最高,到进展期胃癌时表达最低.在I型增生胃黏膜中的表达率与早期胃癌、进展期胃癌相比,差异均有统计学意义(P均<0.05).MDM2蛋白表达与胃癌淋巴结转移、浸润深度有关.Rb蛋白表达与胃癌临床病理学相关指标间无关.MDM2和Rb在胃癌中的表达呈负相关(P<0.01,γs=-0.475).干涉mdm2后可以明显抑制细胞的增殖.结论:MDM2,Rb的表达可作为判断胃癌生物学行为的一个指标,对预后有一定的指导意义;特异性降低mdm2的表达可以作为胃癌治疗的一个分子靶点.
AIM： To investigate the roles of mdm2 and Rb genes in gastric mucosal carcinogenesis and the relation between their expressions and the biological behavior of gastric carcinoma. METHODS： Normal mucusa （ n = 18 ）, slight dysplasia （ n = 10 ）, moderate and severe dysplasia （ n = 16）, early gastric carcinoma （n = 18）, advanced gastric carcinoma （n = 38 ） were detected for MDM2 and Rb expressions by immunohistochemical streptavidin-peroxidase staining （S-P method ）. In view of these data, we reduced the expression of mdm2 in SGC-7901 cells by RNAi and observed the consequent effects on cell proliferation. RESULTS： The positive rates of MDM2 protein were 33.3% , 40.0%, 43.8%, 55.6%, and 57.9% in normal mucosa, slight hyperplasia, moderate and severe dysplasia, early gastric carcinoma and advanced cases, respectively, and that of Rb protein 94.4%, 100.0%, 81.3%, 55.6%, and 63.2%, respectively. We observed that MDM2 protein expressed with visible crescendo tendency from normal gastric mucosa to hyperplasia and carcinoma, while the positive rates of Rb protein decreased gradually with the progression of lesion. The positive rate of Rb protein in slight dysphasia was obviously higher than that of early and advanced gastric carcinoma （ P 〈 0.05, respectively）. The expression of MDM2 protein in gastric carcinoma was positively correlated with the depth of invasion and lymph node metastasis （P 〈0.05, P 〈 0.01 ）. Besides, MDM2 expression was negatively correlated with Rb expression in gastric carcinoma （γs = -0.475, P 〈 0.01 ）. In addition, cell proliferation was significandy inhibited in mdm2 kockdown cells. CONCLUSION： The expression of MDM2 protein is of clinical significance to evaluate the biological behavior of gastric carcinoma. Rb protein can be used as a marker to predict the occurrence of early gastric carcinoma.
出处
《第四军医大学学报》
北大核心
2007年第23期2122-2125,共4页
Journal of the Fourth Military Medical University
