胃癌组织中caveolin-1和E-cadherin表达及相关性的研究

Expression and correlation of caveolin-1 and E-cadherin in gastric cancer

背景与目的:胃癌组织中caveolin-1、E-cadherin表达的相关性不是很清楚。本研究通过分析不同分化程度的胃癌组织中caveolin-l和E-cadherin的表达,探讨两者间相关性及其在胃癌发展过程中可能发挥的作用。方法:本研究所选取的组织点的构成如下:3例相对正常黏膜,24例癌前病变组织(慢性萎缩性胃炎和肠上皮化生各12例),65例胃癌组织和22例淋巴结转移灶。按Lauren分类法将上述癌组织分为肠型胃癌和弥漫型胃癌。应用免疫组织化学方法检测E-cadherin、caveolin-1在不同类型胃组织中的表达与分布。进一步应用RT-PCR、Western blot及双标记免疫荧光检测E-cadherin、caveolin-1在胃癌细胞系中的表达。结果:胃癌组织与癌前病变相比,细胞膜上的E-cadherin表达明显减少(P<0.01),而caveolin-1的表达无差异(P>0.05)。细胞膜上的caveolin-1、E-cadherin在弥漫型胃癌中的表达水平明显低于在肠型胃癌中的表达(P<0.01)。在淋巴结转移灶中,caveolin-1在细胞膜上的表达率为90.9%(20/22),E-cadherin则为18.2%(4/22)。在肠型胃癌和弥漫型胃癌细胞的细胞膜上,caveolin-1和E-cadherin的表达无相关性。肠型胃癌细胞的细胞质caveolin-1和E-cadherin的表达之间无相关性。弥漫型胃癌细胞的细胞质中caveolin-1与E-cadherin的表达呈正相关(r=0.642,P<0.01)。在胃癌细胞膜上或细胞质中未观察到caveo1in-1和E-cadherin有明确的相同的位置关系。AGS、HGC-27、MGC803和BGC823四个胃癌细胞系中,caveolin-1与E-cadherin的mRNA含量及其相应的蛋白表达高低并不一致。结论:caveolin-1和E-cadherin的表达无显著相关性。E-cadherin在多阶段胃癌发生过程中的下调甚至缺失或许与caveolin-1介导的内吞途径无关。

Background and purpose： The correlation between expression of caveolin-1 and E-cadherin remains unclear in gastric cancer. In order to understand the correlation between caveolin-1 and E-cadherin and their role in the development of gastric cancer, this study analyzed their expression in well or poorly differentiated gastric cancers. Methods： Expression of caveolin-1 and E-cadherin in different gastric cancers were detected using immunohistochemistry. Expressions of caveolin-1 and E-cadherin in gastric cancer cell lines were detected by using RT-PCR, Western blot and double-labeling immunofluorescence assay. Results： Membranous E-cadherin expression in gastric cancer tissues decreased significantly in comparison to those in the precancerous lesions （P〈0.01）. However, membranous caveolin-1 expression in gastric cancer tissues did not differ significantly from that in precancerous lesions （P〉0.05）. Expression of membranous E-cadherin and caveolin-1 in diffuse-type gastric cancer tissues decreased significantly compared with that in intestinal-type gastric cancer tissues （P〈0.01）. Positive in 22 lymph node metastatic focuses were 90.9% of membranous caveolin-1 expression and 18.2% of membranous E-cadherin expression. A correlative analysis between membranous caveolin-1 expression and membranous E-cadherin expression showed no statistical significance in intestinal-type gastric cancer tissues and in diffuse-type gastric cancer tissues. However, there was a positive correlation between cytosolic caveolin-1 and E-cadhefin in diffuse-type gastric cancer tissues （r=0.642,P〈0.01）. The specific histological co-localization of caveolin-1 and E-cadherin could not be observed. The expression of E-cadherin was not in accordance with the expression of caveolin-1 at both mRNA and protein levels in four human gastric cancer cell lines （AGS, HGC-27, MGC803 and BGC823）. Conclusion： There is evident correlation between expression of caveolin-1 and E-cadherin in gastric cancer. The down regulation or loss of E-cadherin in different stages of gastric cancer might not correlate with endocytosis mediated by caveolin-1.