Prostate cancer cells differ in testosterone accumulation, dihydrotestosterone conversion, and androgen receptor signaling response to steroid 5α-reductase inhibitors

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dc.contributor.authorWu, Yue
dc.contributor.authorGodoy, Alejandro
dc.contributor.authorAzzouni, Faris
dc.contributor.authorWilton, John H.
dc.contributor.authorIp, Clement
dc.contributor.authorMohler, James L.
dc.date.accessioned2025-01-24T00:08:51Z
dc.date.available2025-01-24T00:08:51Z
dc.date.issued2013
dc.description.abstractBACKGROUND. Blocking 5-reductase-mediated testosterone conversion to dihydrotestosterone (DHT) with finasteride or dutasteride is the driving hypothesis behind two prostate cancer prevention trials. Factors affecting intracellular androgen levels and the androgen receptor (AR) signaling axis need to be examined systematically in order to fully understand the outcome of interventions using these drugs.
dc.description.abstractMETHODS. The expression of three 5-reductase isozymes, as determined by immunohistochemistry and qRT-PCR, was studied in five human prostate cancer cell lines. Intracellular testosterone and DHT were analyzed using mass spectrometry. A luciferase reporter assay and AR-regulated genes were used to evaluate the modulation of AR activity.
dc.description.abstractRESULTS. Prostate cancer cells were capable of accumulating testosterone to a level 15-50 times higher than that in the medium. The profile and expression of 5-reductase isozymes did not predict the capacity to convert testosterone to DHT. Finasteride and dutasteride were able to depress testosterone uptake in addition to lowering intracellular DHT. The inhibition of AR activity following drug treatment often exceeded the expected response due to reduced availability of DHT. The ability to maintain high intracellular testosterone might compensate for the shortage of DHT.
dc.description.abstractCONCLUSIONS. The biological effect of finasteride or dutasteride appears to be complex and may depend on the interplay of several factors, which include testosterone turnover, enzymology of DHT production, ability to use testosterone and DHT interchangeably, and propensity of cells for off-target AR inhibitory effect. (c) 2013 Wiley Periodicals, Inc.
dc.fuente.origenWOS
dc.identifier.doi10.1002/pros.22694
dc.identifier.eissn1097-0045
dc.identifier.issn0270-4137
dc.identifier.urihttps://doi.org/10.1002/pros.22694
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/101969
dc.identifier.wosidWOS:000323110000010
dc.issue.numero13
dc.language.isoen
dc.pagina.final1482
dc.pagina.inicio1470
dc.revistaProstate
dc.rightsacceso restringido
dc.subjectprostate cancer
dc.subjectandrogen receptor
dc.subjectsteroid 5 alpha-reductase
dc.subjecttestosterone
dc.subjectdihydrotestosterone
dc.subjectdutasteride
dc.subjectfinasteride
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleProstate cancer cells differ in testosterone accumulation, dihydrotestosterone conversion, and androgen receptor signaling response to steroid 5α-reductase inhibitors
dc.typeartículo
dc.volumen73
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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