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Article: Melatonin MT 1 receptor-induced transcriptional up-regulation of p27 Kip1 in prostate cancer antiproliferation is mediated via inhibition of constitutively active nuclear factor kappa B (NF-κB): Potential implications on prostate cancer chemoprevention and therapy

TitleMelatonin MT 1 receptor-induced transcriptional up-regulation of p27 Kip1 in prostate cancer antiproliferation is mediated via inhibition of constitutively active nuclear factor kappa B (NF-κB): Potential implications on prostate cancer chemoprevention and therapy
Authors
KeywordsMelatonin
Mt 1 Receptor
Nuclear Factor Kappa B
P27 Kip1
Prostate
Issue Date2013
PublisherBlackwell Munksgaard. The Journal's web site is located at http://www.blackwellpublishing.com/journals/JPI
Citation
Journal Of Pineal Research, 2013, v. 54 n. 1, p. 69-79 How to Cite?
AbstractOur laboratory has recently demonstrated a melatonin MT 1 receptor-mediated antiproliferative signaling mechanism in androgen receptor (AR)-positive prostate epithelial cells which involves up-regulation of p27 Kip1 through dual activation of Gα s/protein kinase A (PKA) and Gα q/protein kinase C (PKC) in parallel, and down-regulation of activated AR signaling via PKC stimulation. The aim of the present investigation was to identify the transcription factor that mediates melatonin's up-regulatory effect on p27 Kip1 in LNCaP and 22Rv1 prostate cancer cells. Deletion mapping and reporter assays of the p27 Kip1 promoter revealed that the putative melatonin-responsive transcription factor binds to a 116 base-pair region of the promoter sequence, which contains a potential nuclear factor kappa B (NF-κB) binding site. When the NF-κB binding site was abolished by site-directed mutagenesis, the stimulatory effect of melatonin on p27 Kip1 promoter activity was mitigated. Notably, melatonin inhibited the DNA binding of activated NF-κB via MT 1 receptor-induced PKA and PKC stimulation. Furthermore, melatonin's up-regulatory effect on p27 Kip1 transcription and consequent cell antiproliferation were abrogated by NF-κB activator but mimicked by NF-κB inhibitor. The results indicate that inhibition of constitutively active NF-κB via melatonin MT 1 receptor-induced dual activation of (Gα s) PKA and (Gα q) PKC can de-repress the p27 Kip1 promoter leading to transcriptional up-regulation of p27 Kip1. MT 1 receptor-mediated inhibition of activated NF-κB signaling provides a novel mechanism supporting the use of melatonin in prostate cancer chemoprevention and therapy. © 2012 John Wiley & Sons A/S.
Persistent Identifierhttp://hdl.handle.net/10722/171796
ISSN
2015 Impact Factor: 9.314
2015 SCImago Journal Rankings: 2.655
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorShiu, SYWen_US
dc.contributor.authorLeung, WYen_US
dc.contributor.authorTam, CWen_US
dc.contributor.authorLiu, VWSen_US
dc.contributor.authorYao, KMen_US
dc.date.accessioned2012-10-30T06:17:11Z-
dc.date.available2012-10-30T06:17:11Z-
dc.date.issued2013en_US
dc.identifier.citationJournal Of Pineal Research, 2013, v. 54 n. 1, p. 69-79en_US
dc.identifier.issn0742-3098en_US
dc.identifier.urihttp://hdl.handle.net/10722/171796-
dc.description.abstractOur laboratory has recently demonstrated a melatonin MT 1 receptor-mediated antiproliferative signaling mechanism in androgen receptor (AR)-positive prostate epithelial cells which involves up-regulation of p27 Kip1 through dual activation of Gα s/protein kinase A (PKA) and Gα q/protein kinase C (PKC) in parallel, and down-regulation of activated AR signaling via PKC stimulation. The aim of the present investigation was to identify the transcription factor that mediates melatonin's up-regulatory effect on p27 Kip1 in LNCaP and 22Rv1 prostate cancer cells. Deletion mapping and reporter assays of the p27 Kip1 promoter revealed that the putative melatonin-responsive transcription factor binds to a 116 base-pair region of the promoter sequence, which contains a potential nuclear factor kappa B (NF-κB) binding site. When the NF-κB binding site was abolished by site-directed mutagenesis, the stimulatory effect of melatonin on p27 Kip1 promoter activity was mitigated. Notably, melatonin inhibited the DNA binding of activated NF-κB via MT 1 receptor-induced PKA and PKC stimulation. Furthermore, melatonin's up-regulatory effect on p27 Kip1 transcription and consequent cell antiproliferation were abrogated by NF-κB activator but mimicked by NF-κB inhibitor. The results indicate that inhibition of constitutively active NF-κB via melatonin MT 1 receptor-induced dual activation of (Gα s) PKA and (Gα q) PKC can de-repress the p27 Kip1 promoter leading to transcriptional up-regulation of p27 Kip1. MT 1 receptor-mediated inhibition of activated NF-κB signaling provides a novel mechanism supporting the use of melatonin in prostate cancer chemoprevention and therapy. © 2012 John Wiley & Sons A/S.en_US
dc.languageengen_US
dc.publisherBlackwell Munksgaard. The Journal's web site is located at http://www.blackwellpublishing.com/journals/JPIen_US
dc.relation.ispartofJournal of Pineal Researchen_US
dc.subjectMelatoninen_US
dc.subjectMt 1 Receptoren_US
dc.subjectNuclear Factor Kappa Ben_US
dc.subjectP27 Kip1en_US
dc.subjectProstateen_US
dc.titleMelatonin MT 1 receptor-induced transcriptional up-regulation of p27 Kip1 in prostate cancer antiproliferation is mediated via inhibition of constitutively active nuclear factor kappa B (NF-κB): Potential implications on prostate cancer chemoprevention and therapyen_US
dc.typeArticleen_US
dc.identifier.emailShiu, SYW:sywshiu@hkucc.hku.hken_US
dc.identifier.emailLeung, WYG: gwyleung@hkucc.hku.hk-
dc.identifier.emailTam, CW: h9810424@hkucc.hku.hk-
dc.identifier.emailLiu, VWS: vwsliu@hku.hk-
dc.identifier.emailYao, KM: kmyao@hku.hk-
dc.identifier.authorityShiu, SYW=rp00384en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1111/j.1600-079X.2012.01026.xen_US
dc.identifier.pmid22856547-
dc.identifier.scopuseid_2-s2.0-84872684040en_US
dc.identifier.hkuros208405-
dc.identifier.isiWOS:000314848500007-
dc.publisher.placeDenmarken_US
dc.identifier.scopusauthoridShiu, SYW=7005550655en_US
dc.identifier.scopusauthoridLeung, WY=55323997800en_US
dc.identifier.scopusauthoridTam, CW=7201442977en_US
dc.identifier.scopusauthoridLiu, VWS=55324000400en_US
dc.identifier.scopusauthoridYao, KM=55276711500en_US

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