Co-expression and impact of prostate specific membrane antigen and prostate specific antigen in prostatic pathologies

<p>Abstract</p> <p>Background</p> <p>The present study was undertaken to relate the co-expression of prostate-associated antigens, PSMA and PSA, with the degree of vascularization in normal and pathologic (hyperplasia and cancer) prostate tissues to elucidate their possible role in tumor progression.</p> <p>Methods</p> <p>The study was carried out in 6 normal, 44 benign prostatic hyperplastic and 39 cancerous human prostates. Immunohistochemical analysis were performed using the monoclonal antibody CD34 to determine the angiogenic activity, and the monoclonal antibodies 3E6 and ER-PR8 to assess PSMA and PSA expression, respectively.</p> <p>Results</p> <p>In our study we found that in normal prostate tissue, PSMA and PSA were equally expressed (3.7 ± 0.18 and 3.07 ± 0.11). A significant difference in their expression was see in hyperplastic and neoplastic prostates tissues (16.14 ± 0.17 and 30.72 ± 0.85, respectively) for PSMA and (34.39 ± 0.53 and 17.85 ± 1.21, respectively) for PSA. Study of prostate tumor profiles showed that the profile (PSA+, PSMA-) expression levels decreased between normal prostate, benign prostatic tissue and primary prostate cancer. In the other hand, the profile (PSA-, PSMA+) expression levels increased from normal to prostate tumor tissues. PSMA overexpression was associated with high intratumoral angiogenesis activity. By contrast, high PSA expression was associated with low angiogenesis activity.</p> <p>Conclusion</p> <p>These data suggest that these markers are regulated differentially and the difference in their expression showed a correlation with malignant transformation. With regard to the duality PSMA-PSA, this implies the significance of their investigation together in normal and pathologic prostate tissues.</p

Insight into the heterogeneity of prostate cancer through PSA-PSMA prostate clones: mechanisms and consequences

A major clinical challenge is posed by the current inability to readily distinguish indolent from aggressive tumors in prostate cancer patients. Research efforts are dedicated to overcome this problem by understanding the molecular basis of the transition from normal, benign cells to prostatic intraepithelial neoplasia (PIN), localized carcinoma, and metastatic cancer. Combined with the evidence of the phenotypic heterogeneity of benign prostate hyperplasia, primary tumors and metastases, it is conceivable that several prostate clones emerge progressively during tumor progression. We have identified several PSA-PSMA prostate clones during prostate cancer progression. In this paper we focus on the susceptibilities of these PSAPSMA prostate clones to factors that promote prostate hyperplastic, neoplastic and metastatic development and their consequences in disease outcome

A Comparison of the Biological Features of Prostate Cancer with (PSA+, PSMA+) Profile according to RKIP

Purpose. To investigate differences in the biological features of the most immunoexpressed prostate cancer (PC) profiles (PSA+, PSMA+) according to the RKIP. Methods. 19 PC with dominant Gleason grade ≥8 were studied. Expression of PSA, PSMA, RKIP, Raf-1, MEK-1, ERK-1, ERK-2, p-Akt (T308), p-Akt (S473), NF-κB p50, and NF-κBp65 were detected immunohistochemically. Results. Loss of RKIP in the most immunoexpressed PC (PSA+, PSMA+) profile was associated with increased levels of PSA and PSMA expression. Intensities of immunoreactions to PSA and PSMA were higher in cancer cells negative for RKIP (12.51 ± 1.6 and 34.95 ± 1.92) compared to those positive for RKIP (4.68 ± 1.11 and 28.56 ± 0.91). In parallel, missing RKIP expression in PC patients with PSA+, PSMA+ profile was connected with increased components of both Raf-1/MEK/ERK and NF-κB (p65/p50), whereas Akt is activated independently of RKIP. Conclusions. Although characterized by the same (PSA+, PSMA+) profile, PC phenotype missing the RKIP related to invasive potential and greater biological aggressiveness reflected in overexpression of components of Raf-1/MEK/ERK and NF-κB (p65/p50) in which Akt is activated independently of RKIP. Taking into account the PC phenotypes according to RKIP among PSA-PSMA profiles may improve distinguishing them from cancers that will become more aggressive and therefore adapt the therapeutic strategies in those patients

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Western blotting analysis was performed. Western Blotting analysis revealed immunoexpression of TRAF-2, ASK-1, MEK-6 and Pp38 in BPH and PC. MEK-6 and NF-ÎB/p65 were absent in NP. Immunohistochemical analysis showed significant weak optical density to ASK-1 in PC compared to NP and BPH. Optical densities to MEK-6 and NF-ÎB/p65 were significantly intense in PC. p38 activation in prostate cancer could have apoptotic and proliferation role depending on the activation of its upstream and downstream component