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Article: Inhibition of prostate cancer cell growth by human secreted PDZ domain-containing protein 2, a potential autocrine prostate tumor suppressor

TitleInhibition of prostate cancer cell growth by human secreted PDZ domain-containing protein 2, a potential autocrine prostate tumor suppressor
Authors
Issue Date2006
PublisherThe Endocrine Society. The Journal's web site is located at http://endo.endojournals.org
Citation
Endocrinology, 2006, v. 147 n. 11, p. 5023-5033 How to Cite?
AbstractA possible role of the PDZ domain-containing protein 2 (PDZD2) in prostate tumorigenesis has been suggested. Besides, PDZD2 is posttranslationally cleaved by a caspase-dependent mechanism to form a secreted PDZ domain-containing protein 2 (sPDZD2) with unknown functions in humans. In this study, we demonstrate the endogenous expression of PDZD2 and secretion of sPDZD2 in cancerous DU145, PC-3, 22Rv1, LNCaP, and immortalized RWPE-1 prostate epithelial cells. Inhibition of endogenous sPDZD2 production and secretion by DU145, PC-3, 22Rv1, and RWPE-1 cells via the caspase-3 inhibitor Z-DEVD-FMK resulted in increased cell proliferation, which was abrogated by treatment with exogenous recombinant sPDZD2. Whereas sPDZD2-induced antiproliferation in DU145, PC-3, and 22Rv1 cells, it induced apoptosis in LNCaP cells. The data suggest that endogenous sPDZD2, produced by caspase-3-mediated cleavage from PDZD2, may function as a novel autocrine growth suppressor for human prostate cancer cells. The antiproliferative effect of sPDZD2 was apparently mediated through slowing the entry of DU145, PC-3, and 22Rv1 cells into the S phase of the cell cycle. In DU145 cells, this can be attributed to stimulated p53 and p21 CIP1/WAF1 expression by sPDZD2. On the other hand, the apoptotic effect of sPDZD2 on LNCaP cells was apparently mediated via p53-independent Bad stimulation. Together our results indicate the presence of p53-dependent and p53-independent PDZD2/sPDZD2 autocrine growth suppressive signaling pathways in human prostate cancer cells and suggest a novel therapeutic approach of harnessing the latent tumor-suppressive potential of an endogenous autocrine signaling protein like sPDZD2 to inhibit prostate cancer growth. Copyright © 2006 by The Endocrine Society.
Persistent Identifierhttp://hdl.handle.net/10722/54245
ISSN
2015 Impact Factor: 4.159
2015 SCImago Journal Rankings: 2.363
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTam, CWen_HK
dc.contributor.authorCheng, ASen_HK
dc.contributor.authorMa, RYMen_HK
dc.contributor.authorYao, KMen_HK
dc.contributor.authorShiu, SYWen_HK
dc.date.accessioned2009-04-03T07:40:57Z-
dc.date.available2009-04-03T07:40:57Z-
dc.date.issued2006en_HK
dc.identifier.citationEndocrinology, 2006, v. 147 n. 11, p. 5023-5033en_HK
dc.identifier.issn0013-7227en_HK
dc.identifier.urihttp://hdl.handle.net/10722/54245-
dc.description.abstractA possible role of the PDZ domain-containing protein 2 (PDZD2) in prostate tumorigenesis has been suggested. Besides, PDZD2 is posttranslationally cleaved by a caspase-dependent mechanism to form a secreted PDZ domain-containing protein 2 (sPDZD2) with unknown functions in humans. In this study, we demonstrate the endogenous expression of PDZD2 and secretion of sPDZD2 in cancerous DU145, PC-3, 22Rv1, LNCaP, and immortalized RWPE-1 prostate epithelial cells. Inhibition of endogenous sPDZD2 production and secretion by DU145, PC-3, 22Rv1, and RWPE-1 cells via the caspase-3 inhibitor Z-DEVD-FMK resulted in increased cell proliferation, which was abrogated by treatment with exogenous recombinant sPDZD2. Whereas sPDZD2-induced antiproliferation in DU145, PC-3, and 22Rv1 cells, it induced apoptosis in LNCaP cells. The data suggest that endogenous sPDZD2, produced by caspase-3-mediated cleavage from PDZD2, may function as a novel autocrine growth suppressor for human prostate cancer cells. The antiproliferative effect of sPDZD2 was apparently mediated through slowing the entry of DU145, PC-3, and 22Rv1 cells into the S phase of the cell cycle. In DU145 cells, this can be attributed to stimulated p53 and p21 CIP1/WAF1 expression by sPDZD2. On the other hand, the apoptotic effect of sPDZD2 on LNCaP cells was apparently mediated via p53-independent Bad stimulation. Together our results indicate the presence of p53-dependent and p53-independent PDZD2/sPDZD2 autocrine growth suppressive signaling pathways in human prostate cancer cells and suggest a novel therapeutic approach of harnessing the latent tumor-suppressive potential of an endogenous autocrine signaling protein like sPDZD2 to inhibit prostate cancer growth. Copyright © 2006 by The Endocrine Society.en_HK
dc.languageengen_HK
dc.publisherThe Endocrine Society. The Journal's web site is located at http://endo.endojournals.orgen_HK
dc.relation.ispartofEndocrinologyen_HK
dc.rightsEndocrinology. Copyright © The Endocrine Society.en_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAdaptor Proteins, Signal Transducing - analysis - physiologyen_HK
dc.subject.meshApoptosisen_HK
dc.subject.meshCaspasesc - antagonists & inhibitorsen_HK
dc.subject.meshNeoplasm Proteins - analysis - physiologyen_HK
dc.subject.meshProstatic Neoplasms - pathology - prevention & controlen_HK
dc.titleInhibition of prostate cancer cell growth by human secreted PDZ domain-containing protein 2, a potential autocrine prostate tumor suppressoren_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0013-7227&volume=147&issue=11&spage=5023&epage=5033&date=2006&atitle=Inhibition+of+prostate+cancer+cell+growth+by+human+secreted+PDZ+domain-containing+protein+2,+a+potential+autocrine+prostate+tumor+suppressoren_HK
dc.identifier.emailYao, KM: kmyao@hku.hken_HK
dc.identifier.emailShiu, SYW: sywshiu@hkucc.hku.hken_HK
dc.identifier.authorityYao, KM=rp00344en_HK
dc.identifier.authorityShiu, SYW=rp00384en_HK
dc.description.naturepostprinten_HK
dc.identifier.doi10.1210/en.2006-0207en_HK
dc.identifier.pmid16873542-
dc.identifier.scopuseid_2-s2.0-33751254373en_HK
dc.identifier.hkuros124800-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33751254373&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume147en_HK
dc.identifier.issue11en_HK
dc.identifier.spage5023en_HK
dc.identifier.epage5033en_HK
dc.identifier.eissn1945-7170-
dc.identifier.isiWOS:000241324900003-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridTam, CW=7201442977en_HK
dc.identifier.scopusauthoridCheng, AS=21733421700en_HK
dc.identifier.scopusauthoridMa, RYM=8323783700en_HK
dc.identifier.scopusauthoridYao, KM=7403234578en_HK
dc.identifier.scopusauthoridShiu, SYW=7005550655en_HK

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