Amplification of chromosome band 11q13 and a role for cyclin D1 in human breast cancer

The role of p27Kip1 in gamma interferon-mediated growth arrest of mammary epithelial cells and related defects in mammary carcinoma cells

“…Recent evidence suggests that over-expression of cyclin D1 or cyclin E causes an up-regulation of p27 protein as part of a self-regulatory feedback Sgambato et al, 1996). Our results show that cyclin E and cdk2 are expressed at considerably higher levels in carcinoma cell lines than in MECs ( Figure 7a), and others have shown ampli®cation or overexpression of either cyclin D or cyclin E in a signi®cant percentage of primary mammary carcinomas (Wang et al, 1994;Dickson et al, 1995;Peters et al, 1995). These ®ndings suggest that the overexpression of positive growth regulators may overcome the ability of the feedback to stimulate su cient p27 expression for adequate control of cdk2 kinase activity.…”

Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK–mediated activation of the p16Ink4a-p19Arf pathway

“…A primary implication of our findings is that transformation caused by overexpression or amplification of cyclin D1, Erbb2 or Hras1 will be attenuated by depletion or inactivation of Wip1. CCND1 (encoding cyclin D1) is amplified in ∼20% of human breast cancers 23 , and overexpression of cyclin D1 has been reported for >50% of human mammary carcinomas 24,25 . Likewise, amplification or overexpression of Erbb2 has been documented in ∼50% of human breast cancers 26 , and PPM1D is amplified in up to 18% of primary human breast tumors 3,12 .…”

BRCA1 gene in breast cancer

“…Sporadic breast cancers exhibit a relatively high frequency of HER2/neu and cyclin D1 gene amplification (20-25% and 15-20%, respectively), as demonstrated by FISH (fluorescent in situ hybridization) analysis (Pavelic et al, 1992;Dickson et al, 1995;Barnes and Gillett, 1998;Spyratos et al, 2000;Lohrisch and Piccart, 2001). The incidence of over-expression of the HER2/neu and cyclin D1 proteins is even higher (about 25-30% and 30-40%, respectively); and these two genes are thought to function as essential oncogenes during the development of a subset of human breast cancer cases (reviewed in Barnes and Gillett, 1998;Lohrisch and Piccart, 2001).…”