Hurlstone A F, Reid G, Reeves J R, Fraser J, Strathdee G, Rahilly M, Parkinson E K, Black D M
Beatson Institute for Cancer Research, CRC Beatson Laboratories, Bearsden, Glasgow, UK.
Oncogene. 1999 Mar 11;18(10):1881-90. doi: 10.1038/sj.onc.1202491.
We identified CAVEOLIN-1 as a candidate for a tumour suppressor gene mapping to human chromosome 7q31.1. A number of studies suggest that caveolin could function as a tumour suppressor. Expression of caveolin, and in turn the number of caveolae within a cell, are inversely correlated with the transforming ability of numerous oncoproteins, including H-ras, v-abl, and bcr-abl, and caveolin is a major transformation-dependent substrate of v-src. Heterologous expression of caveolin has been shown to abrogate anchorage-independent growth and induce apoptosis in transformed fibroblasts and also to suppress anchorage-independent growth in human mammary carcinoma cells. We have analysed the status and expression of the human CAVEOLIN-1 gene in primary tumours and tumour-derived cell lines. We found no evidence for mutation of CAVEOLIN-1 in human cancers. Additionally, we found that while the first two exons of CAVEOLIN-1 are associated with a CpG island, this is not methylated in either primary tumours or in tumour-derived cell lines in which Caveolin-1 expression is low or undetectable. The level of expression of Caveolin-1 does not correlate with loss of heterozygosity at the CAVEOLIN-1 locus in these same cell lines. Contrary to other published studies, we have shown that CAVEOLIN-1 is not expressed in normal breast ductal epithelial cells in vivo. CAVEOLIN-1 is however highly expressed in breast myoepithelial cells and its expression is retained in tumours derived from breast myoepithelium. Together our data refute a role for CAVEOLIN-1 as a breast tumour suppressor gene in vivo.
我们确定小窝蛋白-1（CAVEOLIN-1）是一个肿瘤抑制基因候选物，定位于人类染色体7q31.1。多项研究表明，小窝蛋白可能发挥肿瘤抑制作用。小窝蛋白的表达以及细胞内小窝的数量，与包括H-ras、v-abl和bcr-abl在内的多种癌蛋白的转化能力呈负相关，并且小窝蛋白是v-src主要的转化依赖性底物。已表明小窝蛋白的异源表达可消除转化成纤维细胞的非锚定依赖性生长并诱导其凋亡，还可抑制人乳腺癌细胞的非锚定依赖性生长。我们分析了原发性肿瘤和肿瘤衍生细胞系中人类CAVEOLIN-1基因的状态和表达。我们没有发现人类癌症中CAVEOLIN-1发生突变的证据。此外，我们发现虽然CAVEOLIN-1的前两个外显子与一个CpG岛相关，但在原发性肿瘤或小窝蛋白-1表达低或无法检测到的肿瘤衍生细胞系中，该区域均未发生甲基化。在这些相同的细胞系中，小窝蛋白-1的表达水平与CAVEOLIN-1基因座的杂合性缺失无关。与其他已发表的研究相反，我们已表明CAVEOLIN-1在体内正常乳腺导管上皮细胞中不表达。然而，CAVEOLIN-1在乳腺肌上皮细胞中高度表达，并且其表达在源自乳腺肌上皮的肿瘤中得以保留。我们的数据共同反驳了CAVEOLIN-1在体内作为乳腺肿瘤抑制基因的作用。
