Wu Ping, Wang Xiaohui, Li Fei, Qi Baoju, Zhu Hua, Liu Shuang, Cui Yeqing, Chen Jianwen
Center for Systems Biology, Institute of Biophysics, Chinese Academy of Sciences, Datun Road 15, Chaoyang District, Beijing 100101, China.
Biochem Biophys Res Commun. 2008 Nov 7;376(1):215-20. doi: 10.1016/j.bbrc.2008.08.146. Epub 2008 Sep 7.
Caveolin-1 is an essential structural constituent of caveolae membrane domains that has been implicated in mitogenic signaling and oncogenesis. However, the exact functional role of caveolin-1 still remains controversial. In this report, utilizing MCF-7 human breast adenocarcinoma cells stably transfected with caveolin-1 (MCF-7/cav-1 cells), we demonstrate that caveolin-1 expression dramatically inhibits invasion and migration of these cells. Importantly, in vivo experiments employing xenograft tumor models demonstrated that expression of caveolin-1 results in significant growth inhibition of breast tumors. Moreover, a dramatic delay in tumor progression was observed in MCF-7/cav-1 cells as compared with MCF-7 cells. Histological analysis of tumor sections demonstrated a marked decrease in the percentage of proliferating tumor cells (Ki-67 assay) along with an increase in apoptotic tumor cells (TUNEL assay) in MCF-7/cav-1-treated animals. Our current findings provide for the first time in vivo evidence that caveolin-1 can indeed function as a tumor suppressor in human breast adenocarcinoma derived from MCF-7 cells rather than as a tumor promoter.
小窝蛋白-1是小窝膜结构域的一种重要结构成分，与促有丝分裂信号传导和肿瘤发生有关。然而，小窝蛋白-1的确切功能作用仍存在争议。在本报告中，我们利用稳定转染了小窝蛋白-1的MCF-7人乳腺腺癌细胞（MCF-7/cav-1细胞），证明小窝蛋白-1的表达显著抑制这些细胞的侵袭和迁移。重要的是，采用异种移植肿瘤模型的体内实验表明，小窝蛋白-1的表达导致乳腺肿瘤显著生长抑制。此外，与MCF-7细胞相比，在MCF-7/cav-1细胞中观察到肿瘤进展明显延迟。对肿瘤切片的组织学分析表明，在接受MCF-7/cav-1处理的动物中，增殖肿瘤细胞的百分比（Ki-67检测）显著降低，同时凋亡肿瘤细胞增加（TUNEL检测）。我们目前的研究结果首次在体内证明，小窝蛋白-1在源自MCF-7细胞的人乳腺腺癌中确实可作为肿瘤抑制因子发挥作用，而不是肿瘤促进因子。
