TY - JOUR
T1 - Melatonin as a negative mitogenic hormonal regulator of human prostate epithelial cell growth
T2 - Potential mechanisms and clinical significance
AU - Tam, Chun W.
AU - Chan, Kwok W.
AU - Liu, Vincent W.S.
AU - Pang, Bo
AU - Yao, Kwok Ming
AU - Shiu, Stephen Y.W.
PY - 2008/11
Y1 - 2008/11
N2 - Circannual variation in the human serum levels of prostate-specific antigen, a growth marker of the prostate gland, has been reported recently. The present study was conducted to investigate the role of the photoperiodic hormone melatonin (MLT) and its membrane receptors in the modulation of human prostate growth. Expression of MT1 and MT2 receptors was detected in benign human prostatic epithelial tissues and RWPE-1 cells. MLT and 2-iodomelatonin inhibited RWPE-1 cell proliferation and up-regulated p27 Kip1 gene and protein expression in the cells. The effects of MLT were blocked by the nonselective MT1/MT2 receptor antagonist luzindole, but were not affected by the selective MT2 receptor antagonist 4-phenyl-2-propionamidotetraline. Of note, the antiproliferative action of MLT on benign prostate epithelial RWPE-1 cells was effected via increased p27Kip1 gene transcription through MT 1 receptor-mediated activation of protein kinase A (PKA) and protein kinase C (PKC) in parallel, a signaling process which has previously been demonstrated in 22Rv1 prostate cancer cells. Taken together, the demonstration of the MT1/PKA+PKC/p27Kip1 antiproliferative pathway in benign and malignant prostate epithelial cell lines indicated the potential importance of this MLT receptor-mediated signaling mechanism in growth regulation of the human prostate gland in health and disease. Collectively, our data support the hypothesis that MLT may function as a negative mitogenic hormonal regulator of human prostate epithelial cell growth.
AB - Circannual variation in the human serum levels of prostate-specific antigen, a growth marker of the prostate gland, has been reported recently. The present study was conducted to investigate the role of the photoperiodic hormone melatonin (MLT) and its membrane receptors in the modulation of human prostate growth. Expression of MT1 and MT2 receptors was detected in benign human prostatic epithelial tissues and RWPE-1 cells. MLT and 2-iodomelatonin inhibited RWPE-1 cell proliferation and up-regulated p27 Kip1 gene and protein expression in the cells. The effects of MLT were blocked by the nonselective MT1/MT2 receptor antagonist luzindole, but were not affected by the selective MT2 receptor antagonist 4-phenyl-2-propionamidotetraline. Of note, the antiproliferative action of MLT on benign prostate epithelial RWPE-1 cells was effected via increased p27Kip1 gene transcription through MT 1 receptor-mediated activation of protein kinase A (PKA) and protein kinase C (PKC) in parallel, a signaling process which has previously been demonstrated in 22Rv1 prostate cancer cells. Taken together, the demonstration of the MT1/PKA+PKC/p27Kip1 antiproliferative pathway in benign and malignant prostate epithelial cell lines indicated the potential importance of this MLT receptor-mediated signaling mechanism in growth regulation of the human prostate gland in health and disease. Collectively, our data support the hypothesis that MLT may function as a negative mitogenic hormonal regulator of human prostate epithelial cell growth.
KW - MT receptor
KW - Melatonin
KW - Mitogenic regulator
KW - Prostate
KW - p27
UR - http://www.scopus.com/inward/record.url?scp=53749100168&partnerID=8YFLogxK
U2 - 10.1111/j.1600-079X.2008.00608.x
DO - 10.1111/j.1600-079X.2008.00608.x
M3 - Article
C2 - 18637986
AN - SCOPUS:53749100168
SN - 0742-3098
VL - 45
SP - 403
EP - 412
JO - Journal of Pineal Research
JF - Journal of Pineal Research
IS - 4
ER -
