ABSTRACT
Current diagnostic techniques are inefficient in distinguishing latent and low-risk forms of prostate cancer from high-risk forms. The present study is focused on determination of putative tumor markers of aggressive high-grade forms of prostate cancer. Potential markers were determined in blood sera of 133 patients (82 cases and 51 controls) and in cell lines (Gleason score 9-derived 22Rv1 and normal tissue derived PNT1A) on mRNA and protein levels. Alpha-methylacyl-CoA racemase (AMACR), metallothionein classes 1A and 2A (MT1A and MT2A) were determined and compared to prostate specific antigen (PSA) levels. On mRNA level, significantly increased expression of MT2A (2.4-fold), PSA (2.6-fold) and AMACR (8.4-fold) and insignificantly (1.9-fold) elevated MT1A in 22Rv1 compared to non-tumor PNT1A were determined. On protein level, significant enhancement of free PSA and total PSA in tumor cell line was evident. AMACR protein was 1.5-fold elevated in tumor line (below the level of significance). Contrary to mRNA, significantly (p = 0.01) reduced level of MT protein in tumor lines was determined. In the case of serum level, significantly enhanced MT level (4.5-fold) in patients' sera was found. No significant changes were observed in the case of AMACR. These findings indicate possible alternative role of MT to PSA prostate cancer marker. In addition, level of AMACR is distinctly higher in the Gleason score 9 in serum of patients and MT shows a descending trend in relation to Gleason score.
Subject(s)
Adenocarcinoma/genetics , Biomarkers, Tumor/genetics , Metallothionein/genetics , Prostate-Specific Antigen/genetics , Prostatic Neoplasms/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Adult , Aged , Biomarkers, Tumor/metabolism , Blotting, Western , Case-Control Studies , Humans , Male , Metallothionein/metabolism , Middle Aged , Neoplasm Grading , Prognosis , Prostate-Specific Antigen/metabolism , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , RNA, Messenger/genetics , Racemases and Epimerases/genetics , Racemases and Epimerases/metabolism , Real-Time Polymerase Chain ReactionABSTRACT
In many developed countries, prostate cancer is the most common male tumour disease. The high incidence and mortality requires early diagnosis, differentiation of aggressive, highly malignant forms from clinically silent forms and understanding of the pathogenesis with its typical metabolic aberrancies (if any) in order to develop new targeted therapies. Prostate cells (including prostate cancer cells) are unique in their relation to zinc ions. Prostate tissue can accumulate these ions in up to tenfold higher concentration than other body cells. These ions influence many cellular processes incl. proliferation, differentiation and apoptosis. Prostate cancer cells lack ability to accumulate zinc. Therefore, zinc ions may be expected to play an important role in the disease pathogenesis, in its propagation and metastatic potential of tumour cells. Intracellular zinc levels are regulated by zinc-binding proteins, especially metallothioneins, and zinc transporters. Zinc level regulation dysfunction has been identified in prostate cancer cells and may thus play an important role in the prostate cancer pathogenesis. Moreover, due to its overproduction by prostate tissue, metallothionein serum levels are elevated and can be used as an important tumour marker.
