INVOLVEMENT OF EGF IN MEDROXYPROGESTERONE ACETATE (MPA)-INDUCED MAMMARY-GLAND HYPERPLASIA AND ITS ROLE IN MPA-INDUCED MAMMARY-TUMORS IN BALB C MICE/

In previous papers we have demonstrated that sialoadenectomy inhibited MPA-induced mammary tumorigenesis in BALB/c mice. To further explore the role of EGF in this experimental model, we evaluated its effects o n mammary glands of sialoadenectomized (sialox) MPA-treated female mic e and on tumor growth. MPA-treated sialox mice were injected s.c. (n = 3) or not (n = 6) with 5 mu g EGF every 36 h for 45 days; MPA-treated sham-operated mice were used as controls (n = 6). Mammary glands from sialox MPA-treated mice are considerably less developed as compared w ith sham-operated animals. The exogenous administration of EGF restore s the usual MPA-induced growth pattern of the glands, thus confirming a role for EGF either in mediating or cooperating with MPA in inducing the mammary architectural changes observed in MPA-treated mice. On th e other hand, primary cultures of progestin-dependent (PD) ductal mamm ary adenocarcinoma in vivo tumor lines and of lobular progestin-indepe ndent (PI) tumor lines were used to evaluate the effect of EGF on tumo r growth. In vitro EGF was found to stimulate cell proliferation of lo bular PI tumor cells and of fibroblastic cells from both types of tumo rs at concentrations higher than 0.1-0.5 ng/ml and in the presence of 1-5% of charcoal-stripped fetal calf serum. Conversely, no proliferati ve effects were observed in ductal PD cells under the same experimenta l conditions, regardless of the presence of 10 nM MPA. It can be concl uded that although EGF plays an important role in MPA-induced mammary carcinogenesis, it is not necessary in PD tumor growth. (C) 1998 Elsev ier Science Ireland Ltd.