A mimic of phosphorylated prolactin induces apoptosis by activating AP-1 and upregulating p21/waf1 in human prostate cancer PC3 cells.

A mimic of phosphorylated prolactin (S179D PRL) has been demonstrated to inhibit prostate cancer cell growth in vitro and in vivo; however, the mechanisms involved in this process remain unknown. In this study, we identified that a four-day treatment of S179D PRL (1 μg/ml) in human prostate PC3 cancer cells activated JNK, c-fos and c-jun, and led to apoptosis. We also demonstrated that p21/waf1 was upregulated in cells transfected with the human PRL receptor (S1b) following a four-day incubation with S179D PRL (1 μg/ml). Once the cells were cotransfected with S1b and either c-fos, c-jun or the c-fos/c-jun constructs for 24 h, S17D PRL activated JNK, c-fos and c-jun, and induced apoptosis in the c-fos/c-jun transfected cells. Additionally, S179D PRL upregulated p21 luciferase activity in the cells transfected with the S1b, activating protein-1 (AP-1) (7x) Luc or p21 Luc constructs. SP600125 (25 μM), a JNK blocker, inhibited the upregulation of AP-1 Luc and p21 Luc in the c-fos/c-jun transfected cells. These results demonstrate that S179D PRL activates JNK and AP-1, which leads to p21 upregulation and apoptosis in human prostate PC3 cancer cells.