Human
breast cancer is the predominant
malignancy and the leading cause of
cancer death in women from Western societies. The cause of
breast cancer is still unknown. Recently, the association between human
prolactin (hPRL) activity and
breast cancer has been reemphasized. Biologically active hPRL has been found to be produced locally by
breast cancer cells that contain high levels of PRL receptor. A high incidence of mammary
tumor growth has also been found in transgenic mice overexpressing lactogenic
hormones. More importantly, it has been demonstrated that the receptors for sex
steroids and PRL are coexpressed and cross-regulated. In this study, we report that we have designed and produced a hPRL antagonist,
hPRL-G129R. By using cell proliferation assays, we have demonstrated that: (a) hPRL and E2 exhibited an additive stimulatory effect on human
breast cancer cell (T-47D) proliferation; (b)
hPRL-G129R possessed an inhibitory effect on T-47D cell proliferation; and (c) when
antiestrogen (4-OH-tamoxifen) and anti-PRL (hPRL-G129R) agents were added together, an additive inhibitory effect was observed. We further investigated the mechanism of the inhibitory effects of
hPRL-G129R in four hPRLR positive
breast cancer cell lines. We report that
hPRL-G129R is able to induce apoptosis in all four cell lines in a dose-dependent manner as determined by the
Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. The apoptosis is induced within 2 h of treatment at a dose as low as 50 ng/ml. We hope that the hPRL antagonist could be used to improve the outcome of human
breast cancer therapy in the near future.