Differential expression and function of caveolin-1 in human gastric cancer progression
Differential expression and function of caveolin-1 in human gastric cancer progression
复制标题
DOI：
10.1158/0008-5472.can-07-1125
复制
发表时间：
2007-09-15
期刊：
影响因子：
11.2
通讯作者：
Ebert, Matthias P. A.
中科院分区：
文献类型：
--
作者：
Burgermeister, Elke;Xing, Xiangbin;Ebert, Matthias P. A.
Caveolin-1是Caveolae的支架蛋白，通过与细胞粘附分子和信号受体相互作用而作为肿瘤调节剂。小窝蛋白-1在胃癌发病机制中的作用目前尚不清楚。我们通过共聚焦免疫荧光显微镜和免疫组化显示，41例胃癌患者的活检组织中，非肿瘤性粘膜在小凹上皮细胞和邻近结缔组织中表达小窝蛋白-1。41例患者中仅3例（7%）胃癌细胞表达小窝蛋白-1，且均为肠型。定量PCR和Western blotting证实，与非肿瘤组织相比，19例胃癌患者中有14例（74%）的Caveolin-1 mRNA和13例患者中有7例（54%）的蛋白表达分别降低。在无肿瘤和GC样品中，在非上皮隔室（肌细胞、成纤维细胞、神经周和内皮细胞）中发现了强烈的小窝蛋白-1反应性。在一系列人GC细胞系中，小窝蛋白-1表达在源自原发性肿瘤的细胞（AGS和SNU-1）中低，但在源自远处转移的细胞系（MKN-7、MKN-45、NCI-N87、KATO-III和SNU-5）中增加。小窝蛋白-1在AGS细胞中的异位表达降低了增殖，但促进了锚定非依赖性生长和存活。MKN-45细胞中RNAi介导的内源性小窝蛋白-1的敲低促进细胞生长。这些数据表明，小窝蛋白-1在胃癌中表现出阶段依赖性的差异表达和功能，从而可能有助于其发病机制。
Caveolin-1 is a scaffold protein of caveolae that acts as a tumor modulator by interacting with cell adhesion molecules and signaling receptors. The role of caveolin-1 in the pathogenesis of gastric cancer (GC) is currently unknown. We show by confocal immunofluoreseence microscopy and immunohistochemistry of biopsies from GC patients (n = 41) that the nonneoplastic mucosa expressed caveolin-1 in foveolar epithelia] cells and adjacent connective tissue. GC cells of only 3 of 41 (7%) patients expressed caveolin-1 and were all of the intestinal type. Quantitative PCR and Western blotting confirmed that, compared with nonneoplastic tissue, the overall caveolin-1 mRNA was decreased in 14 of 19 (74%) GC patients and protein in 7 of 13 (54%), respectively. Strong caveolin-1 reactivity was found in the nonepithelial compartment (myocytes, fibroblasts, perineural, and endothelial cells) in both tumor-free and GC samples. In a series of human GC cell lines, caveolin-1 expression was low in cells derived from a primary tumor (AGS and SNU-1) but was increased in cell lines originating from distant metastases (MKN-7, MKN-45, NCI-N87, KATO-III, and SNU-5). Ectopic expression of caveolin-1 in AGS cells decreased proliferation but promoted anchorage-independent growth and survival. RNAi-mediated knockdown of endogenous caveolin-1 in MKN-45 cells accelerated cell growth. These data indicate that caveolin-1 exhibits a stage-dependent differential expression and function in GC and may thereby contribute to its pathogenesis.