PROLACTIN IS A LOCAL GROWTH-FACTOR IN RAT MAMMARY-TUMORS

PRL is a mitogenic hormone that shares many characteristics with growt h factors. The recent demonstration that rat mammary tissue expresses PRL messenger RNA (mRNA) led us to hypothesize that PRL may act as an autocrine/paracrine growth factor in the mammary gland and may be a de terminant in mammary carcinogenesis. To examine this, mammary tumors w ere induced in rats by injection of the carcinogen nitrosomethylurea ( NMU). In vitro studies used a cell line derived from NMU-induced mamma ry tumors. Expression of PRL and PRL receptor was assessed by reverse transcriptase-polymerase chain reaction. The NMU-induced mammary tumor s and the cell line express mRNA for both PRL and PRL receptor (the lo ng and short isoforms); additional hybridizing polymerase chain reacti on products were seen in the tumors, but not in lactating mammary tiss ue. Immunoreactive PRL was detected in the NMU-induced tumors. The eff ect of PRL on cell proliferation was assessed by culturing NMU cells w ith PRL antiserum. The PRL antiserum inhibited cell proliferation by u p to 70% compared to the effect of normal rabbit serum or GH antiserum . In summary, we showed that NMU-induced mammary tumors express mRNA f or PRL and PRL receptor. Addition of PRL antiserum to cultured NMU cel ls significantly inhibited their growth. We propose that PRL may be ac ting as a local growth factor that stimulates the proliferation of mam mary tumors.