Hayashi K, Matsuda S, Machida K, Yamamoto T, Fukuda Y, Nimura Y, Hayakawa T, Hamaguchi M
Department of Molecular Pathogenesis, Nagoya University School of Medicine, Japan.
Cancer Res. 2001 Mar 15;61(6):2361-4.
We looked for mutations in the caveolin-1 gene, encoding a critical molecule for membrane signaling to cell growth, in 92 primary human breast cancers, and we report here the identification of a mutation in caveolin-1 at codon 132 (P132L) in 16% of cases. The mutation-positive cases were mostly invasive scirrhous carcinomas. In cell lines expressing the same mutant of caveolin-1, we observed that the mutant Caveolin-1 expression seemed to induce cellular transformation and activation of mitogen-activated protein kinase-signaling pathway and to promote invasion-ability as well as altered actin networks in the cells. These results provide, for the first time, genetic evidence that a functioning Caveolin-1 mutation may have a role in the malignant progression of human breast cancer.
我们在92例原发性人类乳腺癌中寻找编码细胞生长膜信号关键分子的小窝蛋白-1基因中的突变，在此报告16%的病例中发现小窝蛋白-1第132密码子（P132L）处存在突变。突变阳性病例大多为浸润性硬癌。在表达相同小窝蛋白-1突变体的细胞系中，我们观察到突变型小窝蛋白-1的表达似乎诱导细胞转化和丝裂原活化蛋白激酶信号通路的激活，并促进细胞的侵袭能力以及改变细胞中的肌动蛋白网络。这些结果首次提供了遗传学证据，表明功能性小窝蛋白-1突变可能在人类乳腺癌的恶性进展中起作用。
