Functional consequences of cyclin D1 overexpression in human mammary luminal epithelial cells

The proliferation of eukaryotic cells is primarily regulated by a decision made during the G1 phase of the cell cycle as to remain in the cycle and di vide, or to withdraw from the cycle and adopt a different cell fate. During this time, environmental signals, which regulate the synthesis of the G1 c yclins, are coupled to cell division. In this context, mammalian D-type cyc lins have been shown to control progression through the G1 phase of the mam malian cell cycle. Specifically, cyclin D1 has been reported frequently to be amplified, over-transcribed and overexpressed in human breast carcinomas . Although the effects of cyclin D1 overexpression have been examined in hu man breast carcinoma cell lines, the biological consequences of cyclin D1 e xpression in normal human mammary epithelial cells remain to be elucidated. In this study we have stably over expressed cyclin D1 in human mammary lum inal epithelial cells in order to more directly address the role of cyclin D1 in cell cycle control and tumorigenesis of the human breast, Here, we de monstrate that the effect of cyclin D1 overexpression in these cells is to reduce their growth factor dependency, as well as shorten the duration of G 1 and correspondingly reduce the mean generation time. Collectively, our da ta indicate that deregulation of cyclin D1 expression in human mammary epit helial cells can provide a growth advantage and hence contribute to the onc ogenic potential of these cells, (C) 1998 Kluwer Academic Publishers.