Rat strain-specific actions of 17 beta-estradiol in the mammary gland: Correlation between estrogen-induced lobuloalveolar hyperplasia and susceptibility to estrogen-induced mammary cancers

The genetically related ACI and Copenhagen (COP) rat strains display diamet rically opposed susceptibilities to mammary cancer development when treated chronically with 17 beta-estradiol (E2). Here, we compare the actions of E 2 on cell proliferation and lobuloalveolar development in the mammary gland s of female ACI and COP rats. After 12 wk of E2 treatment, the mammary glan ds of ACI rats exhibited a significantly greater proliferative response to E2, compared with COP rats, as evidenced by quantification of S phase fract ion and development of lobuloalveolar hyperplasia, Focal regions of atypica l epithelial hyperplasia were observed in ACI, but not COP, rats. These str ain differences were not because of differences in circulating E2, progeste rone or, prolactin, Two-thirds of the induced mammary cancers in ACI rats e xhibited aneuploidy. The E2-induced mammary cancers regressed when hormone treatment was discontinued, indicating that they were estrogen-dependent. P rogesterone receptor was expressed by the great majority of epithelial cell s within the E2-induced atypical hyperplastic foci and the mammary carcinom as, suggesting a link between these lesions. These data demonstrate a corre lation between E2 action in the induction of mammary cell proliferation and atypical epithelial hyperplasia and genetically conferred susceptibility t o E2-induced mammary cancers.