Loss of cyclin D1 in concert with deregulated estrogen receptor alpha expression induces DNA damage response activation and interrupts mammary gland morphogenesis.

ABSTRACT: We have previously shown that increased and deregulated estrogen receptor alpha expression in the mammary gland leads to the development of proliferative disease and cancer. To address the importance of cyclin D1 in ERalpha-mediated mammary tumorigenesis, we crossed ERalpha-overexpressing mice with cyclin D1 knockout mice. Mammary gland morphogenesis was completely interrupted in the ERalpha-overexpressing cyclin D1-deficient triple transgenic mice. In addition to a highly significant reduction in mammary epithelial cell proliferation, cyclin E was upregulated resulting in DNA damage checkpoint activation and apoptosis. This imbalance between proliferative and apoptotic rates in conjunction with remarkable structural defects and cellular disorganization in the terminal end buds interrupted

SUBMITTER: Frech MS 

PROVIDER: S-EPMC7007637 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature