Genetic screening reveals an essential role of p27kip1 in restriction of breast cancer progression.

ABSTRACT: The genetic changes and mechanisms underlying the progression of estrogen-dependent breast cancers to estrogen-independent, antiestrogen-resistant, and metastatic breast cancers are unclear despite being a major problem in endocrine therapy. To identify genes responsible for this progression, we carried out a genetic screening by an enhanced retroviral mutagen (ERM)-mediated random mutagenesis in the estrogen-dependent T47D breast cancer cells. We found that T47D cells contain only one p27kip1 (p27) allele coding for the p27 cyclin-dependent kinase (CDK) inhibitor. An ERM insertion into the p27 locus of T47D cells disrupted the p27 gene and created estrogen-independent and antiestrogen-resistant breast cancer cells that still maintained functional estrogen receptors. Disruption of p27 in T

SUBMITTER: Yuan Y 

PROVIDER: S-EPMC2412956 | biostudies-literature | 2007 Sep

REPOSITORIES: biostudies-literature