Inhibition of oncogene STAT3 phosphorylation by a prolactin antagonist, hPRL-G129R, in T-47D human breast cancer cells

We have previously demonstrated that a hPRL antagonist (hPRL-G129R) was abl e to inhibit PRL induced breast cancer cell proliferation through induction of apoptosis. In the present study, we test the hypothesis that the inhibi tory effect of hPRL-G129R in breast cancer cells occurs, at least in part, through the inhibition of oncogene STAT3 activation. We first demonstrated that STAT5 and STAT3 could be activated by either hGH or hPRL in T-47D brea st cancer cells. Although the patterns of STAT5 activation by hGH and hPRL are similar, we observed a nearly 10-fold greater efficacy of hPRL in STAT3 activation as compared to that of hGH. More importantly, we have demonstra ted that activation of STAT3 by hPRL could be inhibited by hPRL-G129R. Sinc e T-47D cells coexpress GHR and PRLR, an attempt was made to dissect the mo lecular events mediated through hGHR or hPRLR using mouse L-cells expressin g a single population of receptors (hGHR or hPRLR). To our surprise, only S TAT5, not STAT3 phosphorylation was observed in these L-cells. In conclusio n, our results suggest that: a) STAT3 is preferably activated through hPRLR in T-47D cells; b) hPRL-G129R is effective in inhibiting STAT3 phosphoryla tion; and c) the mechanism of STAT3 activation is different from that of ST AT5.