title: IMPORTANCE OF APOPTOSIS MARKERS (MDM2, BCL-2 AND Bax) IN BENIGN PROSTATIC HYPERPLASIA AND PROSTATE CANCER.
abstract: MDM2, Bcl-2 and Bax are well recognized markers of apoptosis. The goal of the current study was evaluation of the activity of these markers in different cells of BPH, PCa and hormonally treated prostate cancer (CRPCa) tissues. Activity of the markers has been evaluated in: 39 BPH, 28 prostate cancer (PCa) and 10 castration resistant PCa (CRPCa) tissues. Possible association of intensity of the expression with the disease clinical parameters has been assessed. Activity of MDM2 was higher in PCa and CRPCa as compared with BPH. This difference has been detected in epithelial and vascular prostatic cells. Epithelial activity of Bcl-2 was significantly lower in BPH as compared with PCa and CRPCa. Conversely, intensity of pro-apoptotic protein Bax was significantly higher in PBH than in PCa and CRPCa. The Bax activity in acinar and ductal cells of BPH was positively correlated with age. Intensity of Bcl-2 was significantly increasing, while activity of Bax was decreasing with increasing prostate volume. Significant correlation has been detected with the markers' activity and residual urine. In particular, MDM2 activity was increasing while epithelial activity of Bax was decreasing with increasing residual urine. Serum PSA level was positively correlated with MDM2 and negatively correlated with Bax activity. p27(Kip1) cell cycle inhibitor was positively correlated with Bax but negatively correlated with Bcl-2 activities. Proliferation marker Ki67 was positively correlated with MDM2 and Bcl-2. With increasing Ki67, Bax activity was significantly decreasing. Cyclin D3 was positively correlated with Bax. This pilot study has shown importance of apoptosis markers in BPH and PCa. It is the first study showing complex interrelation between apoptosis and cell cycle regulating proteins in BPH and PCa.
authors.affiliation: A. Tsulukidze National Centre of Urology, Department of Urology, Department of Pathology; Scientific and Practical Center of Clinical Pathology, Tbilisi, Georgia.
authors.forename: Z
authors.initials: Z
authors.lastname: Saker
authors.affiliation: A. Tsulukidze National Centre of Urology, Department of Urology, Department of Pathology; Scientific and Practical Center of Clinical Pathology, Tbilisi, Georgia.
authors.forename: O
authors.initials: O
authors.lastname: Tsintsadze
authors.affiliation: A. Tsulukidze National Centre of Urology, Department of Urology, Department of Pathology; Scientific and Practical Center of Clinical Pathology, Tbilisi, Georgia.
authors.forename: I
authors.initials: I
authors.lastname: Jiqia
authors.affiliation: A. Tsulukidze National Centre of Urology, Department of Urology, Department of Pathology; Scientific and Practical Center of Clinical Pathology, Tbilisi, Georgia.
authors.forename: L
authors.initials: L
authors.lastname: Managadze
authors.affiliation: A. Tsulukidze National Centre of Urology, Department of Urology, Department of Pathology; Scientific and Practical Center of Clinical Pathology, Tbilisi, Georgia.
authors.forename: A
authors.initials: A
authors.lastname: Chkhotua
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division; D056743:Cyclin D3 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D011468:Prostatectomy / Q000379:methods; D011470:Prostatic Hyperplasia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D064129:Prostatic Neoplasms, Castration-Resistant / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden; D051028:bcl-2-Associated X Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C000595707:BCL2 protein, human; D014408:Biomarkers, Tumor; C534696:CCND3 protein, human; D056743:Cyclin D3; D019394:Ki-67 Antigen; C000628856:MKI67 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen