Ataxia telangiectasia mutated (ATM) inhibition transforms human mammary gland epithelial cells.

ABSTRACT: Carriers of mutations in the cell cycle checkpoint protein kinase ataxia telangiectasia mutated (ATM), which represent 1-2% of the general population, have an increased risk of breast cancer. However, experimental evidence that ATM deficiency contributes to human breast carcinogenesis is lacking. We report here that in MCF-10A and MCF-12A cells, which are well established normal human mammary gland epithelial cell models, partial or almost complete stable ATM silencing or pharmacological inhibition resulted in cellular transformation, genomic instability, and formation of dysplastic lesions in NOD/SCID mice. These effects did not require the activity of exogenous DNA-damaging agents and were preceded by an unsuspected and striking increase in cell proliferation also observed in primary hum

SUBMITTER: Mandriota SJ 

PROVIDER: S-EPMC2857118 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature