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

The importance of epidermal growth factor (EGF) in both normal and malignan t mammary gland development are presented in these studies. Initial finding s demonstrated that in the absence of ovarian hormones, EGF had a significa nt proliferative effect on mammary epithelial cells. To determine whether m ammary epithelial cells grown with EGF, in the absence of ovarian hormones, could be transformed by N-methyl-N-nitrosourea (MNU), female ovariectomize d Lewis rats were implanted with pellets containing EGF for 1 week and then treated with MNU for initiation. Two days after MNU treatment, ovaries wer e 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 gr oup (100 %), The mammary cancer morphology of EGF-treated carcinomas was ei ther ductal carcinoma or cribriform adenocarcinoma, whereas intact animals developed mainly papillary and occasional cribriform carcinomas. Fifty-eigh t percent of the carcinomas from the EGF group were ovarian hormone-indepen dent compared with 10% of carcinomas from the intact group. These results d emonstrate that EGF-induced proliferation during initiation with MNU was su fficient to induce the transformation of mammary carcinomas in the absence of ovarian hormones. The hormonal dependency of these EGF-induced carcinoma s were different compared with MNU-initiated mammary carcinomas in intact r ats.