Estrogen Induction of Mammary Cancer in Female ACI Rats

Abstract

Breast cancer is the most prevalent endocrine-related malignancy in women. Both endogenous and exogenous estrogen exposure is associated with an increased breast cancer risk. The main goal of the present research project was to study the early morphological changes and expression of PCNA and ER-a during estrogen induced mammary carcinogenesis in the female ACI rats. The presence of ER-a was further studied by Western blot analysis. The ACI rat is an excellent model to study estrogen-induced mammary cancer, since treatment of estrogen alone induces a high incidence of mammary gland tumors after 5-7 months of treatment. In the present study, ACI female rats were treated with estrogen pellets (5 mg of 17-beta estradiol in a 20-mg pellet) for 4 to 8 months. After 4.5 months of treatment, significant morphological changes were observed when compared to age-matched, untreated controls. The mammary glands of the treated rats displayed dysplastic lesions, and the mammary gland ductules were filled with stratified squamous epithelial cells. Tumors were observed after 6.5 months of estrogen treatment. Immunohistochemical studies indicated the presence of numerous cells positive for proliferating cell nuclear antigen (PCNA) and for estrogen receptor-a (ER). Mammary glands of untreated age-matched rats revealed that most ductule epithelial cells had moderate cytoplasmic and nuclear ER staining, while the mammary glands ofestrogen-treated displayed increased intensity in nuclei ER staining.