Prolactin is a local growth factor in rat mammary tumors

PRL is a mitogenic hormone that shares many characteristics with growth 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 determinant in mammary carcinogenesis. To examine this, mammary tumors were induced in rats by injection of the carcinogen nitrosomethylurea (NMU). In vitro studies used a cell line derived from NMU-induced mammary tumors. Expression of PRL and PRL receptor was assessed by reverse transcriptase-polymerase chain reaction. The NMU-induced mammary tumors and the cell line express mRNA for both PRL and PRL receptor (the long and short isoforms); additional hybridizing polymerase chain reaction products were seen in the tumors, but not in lactating mammary tissue. Immunoreactive PRL was detected in the NMU-induced tumors. The effect of PRL on cell proliferation was assessed by culturing NMU cells with PRL antiserum. The PRL antiserum inhibited cell proliferation by up to 70% compared to the effect of normal rabbit serum or GH antiserum. In summary, we showed that NMU-induced mammary tumors express mRNA for PRL and PRL receptor. Addition of PRL antiserum to cultured NMU cells significantly inhibited their growth. We propose that PRL may be acting as a local growth factor that stimulates the proliferation of mammary tumors.