Induction of mammary carcinomas by N-methyl-N-nitrosourea in ovariectomized rats treated with epidermal growth factor

Abstract

The importance of epidermal growth factor (EGF) in both normal and malignant mammary gland development are presented in these studies. Initial findings demonstrated that in the absence of ovarian hormones, EGF had a significant proliferative effect on mammary epithelial cells. To determine whether mammary epithelial cells grown with EGF, in the absence of ovarian hormones, could be transformed by N-methyl-N-nitrosourea (MNU), female ovariectomized Lewis rats were implanted with pellets containing EGF for 1 week and then treated with MNU for initiation. Two days after MNU treatment, ovaries were implanted and EGF pellets were removed from all ovariectomized groups in order to promote carcinogenesis. The mammary carcinoma incidence of the EGF-stimulated group (90%) was not significantly different from the intact group (100%). The mammary cancer morphology of EGF-treated carcinomas was either ductal carcinoma or cribriform adenocarcinoma, whereas intact animals developed mainly papillary and occasional cribriform carcinomas. Fifty-eight percent of the carcinomas from the EGF group were ovarian hormone-independent compared with 10% of carcinomas from the intact group. These results demonstrate that EGF-induced proliferation during initiation with MNU was sufficient to induce the transformation of mammary carcinomas in the absence of ovarian hormones. The hormonal dependency of these EGF-induced carcinomas were different compared with MNU-initiated mammary carcinomas in intact rats.

N-methyl-N-nitrosourea-induced mammary carcinogenesis is promoted by short-term treatment with estrogen and progesterone mimicking pregnancy in aged female Lewis rats

“…Ovariectomy inhibits the development of mammary carcinomas, indicating that physiological levels of ovarian steroids are required for mammary carcinogenesis (19). However, mammary carcinogenesis can also be effectively suppressed by high physiologic levels of ovarian steroids during pregnancy (5,7), or short-term treatment with pregnancy levels of estrogen and progesterone (8)(9)(10)(11)(12)(13)(14)(15).…”

Genotoxic Effects of Aluminum Chloride and Their Relationship with N-Nitroso-N-Methylurea (NMU)-Induced Breast Cancer in Sprague Dawley Rats

“…Biotery handling conditions were as follows: 12 h light/dark cycles, humidity ranging from 40% to 70%, temperature between 18 • C and 22 • C, and ad libitum access to water and food [32].…”

Impact of C-neu/erbB2 on Estrogen and Estrogen Receptor Alpha-Dependent Proliferation of Mammary Ductal Epithelial Cells

“…To examine the expression patterns of ER and PR, immunolocalization studies were performed on either frozen mammary sections, using an indirect inrnjiunofluorescence assay, or paraffin embedded sections, using immunoperoxidase assay, as previously described (3)(4)(5). For detection of PR, we used the following antibodies: an anti-rabbit polyclonal antibody prepared against mouse PR generated by our laboratory and an antirabbit polyclonal antibody prepared against human PR, purchased from DAKO.…”