title: Nuclear receptors in early hormone refractory prostate cancer and their relationship to apoptosis-related proteins.
abstract: The expression of several genes involved in apoptosis and cell cycle control can be regulated by steroid hormones and related agents via their nuclear receptors. Members of the bcl-2 gene family participate in the regulation of apoptosis in a diverse range of cell types and are implicated in the development of hormone refractory prostate cancer and resistance to anti-cancer therapy. The aim of this study, therefore, was to examine the expression of several nuclear receptors in relation to the expression of apoptosis and cell cycle related proteins in a series of patients with early hormone refractory prostate cancer. Analysis of protein expression revealed only a weak association between Bcl-2 and AR. Bax positivity and p27Kip1 expression were significantly more frequent in the AR-positive tumors, whereas RXRbeta expression was more frequently observed in the AR-negative group. The expression of AR, Bax and p27Kip1 was inversely related, and the expression of RXRbeta directly related, to Gleason pattern status. These results suggest that the immunophenotype of early hormone refractory prostate cancer may be different to that seen in more advanced stage disease. Androgen withdrawal therapy employing anti-androgens may elicit different signalling pathways that may be dependent on ARstatus and ARsensitivity.
authors.affiliation: Laborator of Molecular Pathology; Faculty of Medicine, Palacky University and Faculty Hospital in Olomouc, Olomouc, 77515 Czech Republic. kolarz@tunw.upol.cz
authors.forename: Z
authors.initials: Z
authors.lastname: Kolár
authors.forename: P G
authors.initials: PG
authors.lastname: Murray
authors.forename: J
authors.initials: J
authors.lastname: Madarova
authors.forename: M
authors.initials: M
authors.lastname: Lukesova
authors.forename: A
authors.initials: A
authors.lastname: Hlobilkova
authors.forename: P
authors.initials: P
authors.lastname: Riháková
authors.forename: P
authors.initials: P
authors.lastname: Flavell
authors.forename: M
authors.initials: M
authors.lastname: Strnad
authors.forename: V
authors.initials: V
authors.lastname: Student
authors.forename: B
authors.initials: B
authors.lastname: Vojtesek
mesh_terms: D017209:Apoptosis; D016203:CDC2 Protein Kinase / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008840:Microfilament Proteins / Q000032:analysis; D009124:Muscle Proteins; D011470:Prostatic Hyperplasia / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2; D011944:Receptors, Androgen / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis*; D018168:Receptors, Retinoic Acid / Q000032:analysis; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D008840:Microfilament Proteins; D009124:Muscle Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011944:Receptors, Androgen; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; C058992:Tagln protein, mouse; D051028:bcl-2-Associated X Protein; C082925:retinoic acid receptor beta; D016203:CDC2 Protein Kinase