Activation of estrogen signaling pathways collaborates with loss of Brca1 to promote development of ERalpha-negative and ERalpha-positive mammary preneoplasia and cancer.

ABSTRACT: BRCA1 can regulate estrogen receptor-alpha (ERalpha) activity. This study tested the hypotheses that Brca1 loss in mammary epithelium alters the estrogenic growth response and that exposure to increased estrogen or ERalpha collaborates with Brca1 deficiency to accelerate preneoplasia and cancer development. Longer ductal extension was found in mammary glands of Brca1(f/f;MMTV-Cre) mice during puberty as compared to wild-type mice. Terminal end bud differentiation was impaired in Brca1 mutant mice with preservation of prolactin-induced alveolar differentiation. Exogenous estrogen stimulated an abnormal sustained increase in mammary epithelial cell proliferation and the appearance of ERalpha-negative preneoplasia in postpubertal Brca1 mutant mice. Carcinogenesis was investigated using Brca1(

SUBMITTER: Jones LP 

PROVIDER: S-EPMC3045705 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature