Tumor cell growth inhibition by caveolin re-expression in human breast cancer cells
Tumor cell growth inhibition by caveolin re-expression in human breast cancer cells
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DOI：
10.1038/sj.onc.1201661
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发表时间：
1998-03-19
期刊：
影响因子：
8
通讯作者：
Schnitzer, JE
中科院分区：
文献类型：
--
作者：
Lee, SW;Reimer, CL;Schnitzer, JE
癌症的发生是一个多阶段的过程，其结果是不同基因逐步获得体细胞改变。最近的研究表明，caveolin-1的表达与NIH 3T3细胞的致癌转化水平相关，表明caveolin mag中的caveolin调节正常细胞的增殖。为了更好地了解caveolin-1在癌症发生中的潜在功能，我们已经研究了人乳腺癌细胞中小窝蛋白-1的表达水平，并发现与其正常乳腺上皮对应物相比，小窝蛋白表达在人乳腺癌细胞中显著降低，当将与CMV启动子连接的小窝蛋白cDNA转染到不具有可检测的内源性小窝蛋白的人乳腺癌细胞中时，小窝蛋白-1的过表达导致实质性的生长抑制，如生长速率降低50%和软琼脂中菌落形成降低15倍所示。另外，细胞周期进程中小窝蛋白-1表达的表征表明α-小窝蛋白-1的表达在细胞周期中受到调节，此外，p53缺陷细胞显示小窝蛋白表达的损失。总之，总体表达模式，其在培养物中抑制肿瘤生长的能力，其在细胞周期中的调节，以及p53缺陷细胞中表达的丧失都与小窝蛋白的重要生长调节功能一致，1在正常人乳腺细胞中，需要在致癌转化和肿瘤细胞生长中被抑制。
Cancer development is a multistage process that results from the step-wise acquisition of somatic alterations in diverse genes, Recent studies indicate that caveolin-1 expression correlates with the level of oncogenic transformation in NIH3T3 cells, suggesting that caveolin in caveolae mag regulate normal cell proliferation, In order to better understand potential functions of caveolin-1 in cancer development, we have studied expression levels of caveolin-1 in human breast cancer cells, and have found that caveolin expression is significantly reduced in human breast cancer cells compared with their normal mammary epithelial counterparts, When the caveolin cDNA linked to the CMV promoter is transfected into human mammary cancer cells having no detectable endogenous caveolin, overexpression of caveolin-1 resulted in substantial growth inhibition, as seen by the 50% decrease in growth rate and by similar to 15-fold reduction in colony formation in soft agar, In addition, characterization of caveolin-1 expression during cell cycle progression indicates that expression of alpha-caveolin-1 is regulated during cell cycle, Furthermore p53-deficient cells showed a loss in caveolin expression, In summary, the overall expression patterns, its ability to inhibit tumor growth in culture, its regulation during the cell cycle, and the loss of expression in p53-deficient cells all are consistent with an important growth regulating function for caveolin-1 in normal human mammary cells, that needs to be repressed in oncogenic transformation and tumor cell growth.