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Authordc.contributor.authorClementi, Marisa 
Authordc.contributor.authorSánchez, Catherine 
Authordc.contributor.authorBenítez, Dixan A. 
Authordc.contributor.authorContreras, Héctor R. 
Authordc.contributor.authorHuidobro, Christian 
Authordc.contributor.authorCabezas, Juan 
Authordc.contributor.authorAcevedo, Cristian 
Authordc.contributor.authorCastellón, Enrique A. 
Admission datedc.date.accessioned2019-03-11T12:57:37Z
Available datedc.date.available2019-03-11T12:57:37Z
Publication datedc.date.issued2009
Cita de ítemdc.identifier.citationProstate, Volumen 69, Issue 10, 2009, Pages 1025-1033
Identifierdc.identifier.issn02704137
Identifierdc.identifier.issn10970045
Identifierdc.identifier.other10.1002/pros.20954
Identifierdc.identifier.urihttps://repositorio.uchile.cl/handle/2250/164778
Abstractdc.description.abstractBACKGROUND. Gonadotropin-releasing-hormone (GnRH) analogs are widely used to block hypothalamic–pituitary–gonadal axis and inhibit blood androgen levels in patients with prostate cancer (PCa). In addition, GnRH analogs induce proliferation arrest and apoptosis through GnRH receptors expressed on the membrane of PCa cells. Possible molecular mechanisms involved in GnRH-mediated apoptosis on prostate cancer cells were studied. METHODS. Primary cultures from PCa and benign prostatic hyperplasia (BPH) (nonmalignant control) were derived from samples provided by our Institutional Hospital. Cell cultures were incubated for 24 hr with 20 ng/ml of GnRH agonist Leuprolide (Lp) or antagonist Cetrorelix (Cx). Apoptosis was evaluated by studying the expression of Bax and Bcl-2 and the activation of caspase-9 (intrinsic pathway), caspase-8 (extrinsic pathway), and caspase-3. Also, mRNA level, protein expression and phosphorylation of p53 were studied. RESULTS. Cleaved caspase-8 and -3, but not -9, increased in presence of Lp and Cx in PCa cell cultures. Bax and Bcl-2 mRNA levels showed no changes after GnRH-analog treatments. Only Bax protein showed an increase after Cx treatment in PCa cell cultures. p53 mRNA level was higher in PCa than in BPH cell cultures. Lp and Cx increased p53 expression and phosphorylation in PCa cell cultures. CONCLUSIONS. Apoptosis induced by GnRH analogs seems to be mediated by extrinsic pathway involving p53 phosphorylation. Phosphorylated-p53 might be associated with the increase in apoptotic NGF receptor, p75, previously reported by our laboratory. These findings reinforce the concept of clinical use of GnRH analogs for PCa suggesting that intraprostatic treatment may be more effective.
Lenguagedc.language.isoen
Publisherdc.publisherWiley
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile
Link to Licensedc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
Sourcedc.sourceProstate
Keywordsdc.subjectApoptosis
Keywordsdc.subjectGnRH analogs
Keywordsdc.subjectp53
Keywordsdc.subjectPrimary cell culture
Keywordsdc.subjectProstate cancer
Títulodc.titleGonadotropin releasing hormone analogs induce apoptosis by extrinsic pathway involving p53 phosphorylation in primary cell cultures of human prostatic adenocarcinomas
Document typedc.typeArtículo de revista
Catalogueruchile.catalogadorlaj
Indexationuchile.indexArtículo de publicación SCOPUS
uchile.cosechauchile.cosechaSI


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Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Chile