Stable overexpression of cyclin D1 in a human mammary epithelial cell line prolongs the S-phase and inhibits growth.
Stable overexpression of cyclin D1 in a human mammary epithelial cell line prolongs the S-phase and inhibits growth.
复制标题
DOI：
--
复制
发表时间：
1995-03
期刊：
影响因子：
8
通讯作者：
E. Han;A. Sgambato;Wei Jiang;Zhang Yj;R. Santella;Y. Doki;Cacace Am;I. Schieren;I. Weinstein
中科院分区：
文献类型：
--
作者：
E. Han;A. Sgambato;Wei Jiang;Zhang Yj;R. Santella;Y. Doki;Cacace Am;I. Schieren;I. Weinstein
细胞周期蛋白D1的扩增和/或表达增加出现在相当一部分原发性人类乳腺癌和其他几种类型的人类癌症中。此外，在啮齿动物成纤维细胞中，过表达cyclin D1可促进生长和恶性转化。目前的研究表明，cyclin D1的扩增和表达程度在从正常人乳腺上皮细胞或人乳腺癌细胞中建立的一系列细胞系中差异很大。HBL-100乳腺上皮细胞系未显示cyclin D1的扩增或表达升高。我们使用逆转录病毒介导的转导获得了该细胞系的衍生物，该细胞系稳定表达相对高水平的外源细胞周期蛋白D1 cDNA。这些衍生物表现出加倍时间增加，饱和密度降低，克隆效率降低，非锚定生长降低，s期细胞比例增加，致瘤性降低。因此，在该细胞系中，cyclin D1表达的增加明显抑制而不是促进生长，这可能与s期延长有关。
Amplification and/or increased expression of cyclin D1 occurs in an appreciable fraction of primary human breast carcinomas and several other types of human cancer. In addition, overexpression of cyclin D1 in rodent fibroblasts enhances growth and malignant transformation. The present study demonstrates that the extent of amplification and expression of cyclin D1 varies widely amongst a series of cell lines established from normal human mammary epithelium or human breast carcinomas. The HBL-100 mammary epithelial cell line did not display amplification or increased expression of cyclin D1. We used retrovirus-mediated transduction to obtain derivatives of this cell line that stably expressed relatively high levels of an exogenous cyclin D1 cDNA. These derivatives displayed an increased doubling time, decreased saturation density, decreased cloning efficiency, decreased anchorage-independent growth, an increased fraction of cells in the S-phase, and decreased tumorigenicity. Thus, increased expression of cyclin D1 in this cell line markedly inhibits rather than enhances growth, which may be due to the prolongation of S-phase.