INTERLEUKIN-3 - A PUTATIVE PROTECTIVE FACTOR AGAINST BREAST-CANCER WHICH IS SECRETED BY MALE BUT NOT FEMALE BREAST FIBROBLASTS

The enzyme 17 beta-hydroxysteroid dehydrogenase(17-HSD) is a key regul ator of intracellular 17 beta-estradiol (E2), which is associated with breast cancer and is influenced by paracrine factors released by brea st-cancer fibroblasts. Since the incidence of breast cancer is much hi gher in females than in males, we have used an in vitro cell culture s ystem to investigate whether male fibroblasts may inhibit breast-cance r genesis by restricting the intracellular accumulation of E2. Fibrobl asts were obtained from normal males and females undergoing reduction mammoplasty, and from females with benign or malignant breast lesions. Fibroblast-conditioned medium (CM) was incubated with the established breast-cancer cell line, MCF-7, and its effects on 17-HSD activity we re assessed. CM (25% v/v) from male breast fibroblasts had a significa nt inhibitory effect on reductive 17-HSD, decreasing E2 production. Th is was in direct contrast to the effects of CM from female breast fibr oblasts, which had a powerful stimulatory effect on reductive 17-HSD. RT-PCR allowing simultaneous detection of a range of cytokines was per formed on each type of fibroblast. IL-3 mRNA was consistently detected in fibroblasts from male but not female breast tissue. Addition of rh IL-3 to cultures of MCF-7 caused a reduction in 17-HSD activity and ad dition of a polyclonal antibody directed against IL-3 to male CM compl etely reversed the inhibitory effects of CM. Thus, male breast fibrobl asts may be responsible for secreting IL-3-like factors which, given t he considerably lower incidence rates of breast cancer in men, may hav e a protective effect against breast cancer. (C) 1995 Wiley-Liss, Inc.