[小窝蛋白-1在胃癌中的表达下调及其临床生物学意义]

Gao Xue, Sun Yuan, Huang Lei, Chen Xiao-Yan, Zhang Kai-Li, Kong Qing-You, Liu Jia, Li Hong

Cancer Institute/Liaoning Provincial Key Lab of Cancer Genomics, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, 116027, P.R.China.

Ai Zheng. 2005 Mar;24(3):311-6.

BACKGROUND & OBJECTIVE: Caveolin-1, a candidate tumor suppressor gene, aberrantly expressed in many kinds of carcinomas. This research was designed to check the expression of Caveolin-1 in non-cancerous gastric mucosa, intestinal metaplasia, atypical hyperplasia, gastric cancer tissues, and gastric cancer cell lines MGC803 and BGC823, and to analyze its clinical biological significance in stepwise gastric carcinogenesis.

METHODS

Frozen gastric tissue array-based immunohistochemistry (IHC) was used to examine the expression of Caveolin-1 in 56 specimens of gastric cancer, 29 specimens of non-cancerous mucosa, 11 specimens of intestinal metaplasia, and 7 specimens of atypical hyperplasia. Correlations of Caveolin-1 expression to clinical stage, lymph node metastasis, Lauren's type, and histological type were analyzed. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect mRNA and protein levels of Caveolin-1 in 56 specimens of gastric cancer and relevant adjuvant non-cancerous tissue, and cell lines MGC803 and BGC823.

RESULTS

Positive rate of Caveolin-1 was significantly lower in gastric cancer than in non-cancerous mucosa, intestinal metaplasia, and atypical hyperplasia (17.9% vs. 84.8%, 81.8%, and 57.1%, P<0.05). Positive rate of Caveolin-1 was lower in advanced gastric cancers than in gastric cancer of early stage (16.0% vs. 33.3%), but the difference was not significant (P>0.05). Positive rate of Caveolin-1 was significantly lower in diffuse gastric cancer than in gastric cancer of intestinal type (7.0% vs. 26.9%, P<0.05), significantly lower in the cases with lymph node metastases than in the cases without lymph node metastases (9.7% vs. 31.8%, P<0.05). Protein and mRNA levels of Caveolin-1 in gastric cancer and relevant adjuvant non-cancerous tissues have no significant difference, but its expression was low in MGC803 and BGC823 cells.

CONCLUSION

Progressive down-regulation of Caveolin-1 in gastric epithelial cells is correlated to gastric carcinogenesis.

背景与目的

小窝蛋白-1是一种候选肿瘤抑制基因，在多种癌症中异常表达。本研究旨在检测小窝蛋白-1在非癌性胃黏膜、肠化生、异型增生、胃癌组织以及胃癌细胞系MGC803和BGC823中的表达情况，并分析其在胃癌逐步发生过程中的临床生物学意义。

方法

采用基于冰冻胃组织芯片的免疫组织化学（IHC）方法检测56例胃癌标本、29例非癌性黏膜标本、11例肠化生标本和7例异型增生标本中小窝蛋白-1的表达。分析小窝蛋白-1表达与临床分期、淋巴结转移、Lauren分型和组织学类型的相关性。采用逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹法检测56例胃癌标本及相关癌旁非癌组织、细胞系MGC803和BGC823中小窝蛋白-1的mRNA和蛋白水平。

结果

小窝蛋白-1在胃癌中的阳性率显著低于非癌性黏膜、肠化生和异型增生（17.9%对84.8%、81.8%和57.1%，P<0.05）。进展期胃癌中小窝蛋白-1的阳性率低于早期胃癌（16.0%对33.3%），但差异无统计学意义（P>0.05）。弥漫型胃癌中小窝蛋白-1的阳性率显著低于肠型胃癌（7.0%对26.9%，P<0.05），有淋巴结转移的病例中小窝蛋白-1的阳性率显著低于无淋巴结转移的病例（9.7%对31.8%，P<0.05）。胃癌及相关癌旁非癌组织中小窝蛋白-1的蛋白和mRNA水平无显著差异，但其在MGC803和BGC823细胞中的表达较低。