A mimic of phosphorylated prolactin induces apoptosis by activating AP‑1 and upregulating p21/waf1 in human prostate cancer PC3 cells
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Affiliations: Department of Epidemiology and Health Statistics, School of Public Health and Family Medicine, Capital Medical University, Beijing 100069, P.R. China, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P.R. China
- Published online on: August 23, 2012 https://doi.org/10.3892/ol.2012.876
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1064-1068
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Abstract
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.
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