Revealing the role of zinc(II) in prostate cancer pathogenesis

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Authors

GUMULEC Jaromír SZTALMACHOVÁ Markéta MASAŘÍK Michal KIZEK René

Year of publication 2012
Type Conference abstract
MU Faculty or unit

Faculty of Medicine

Citation
Description Current diagnostic procedures do not enable us to distinguish between clinically latent forms of prostate cancer from aggressive forms, the most common cancer in males. The key to understand the different behavior of these forms is in its molecular mechanisms. Current literature highlights the role of zinc(II) ions in the development and pathogenesis of this cancer. Our objective was to identify diverse metabolical pathways of these forms of cancer and determine prognostic markers of high-grade form of prostate cancer. We determined genes alpha-methylacyl-CoA racemase (AMACR), caveolin-1 (Cav-1), metallothionein (MT), p53, NF-kB, c-FOS, c-JUN, Ki-67, ZIP1 and ZnT-1 on RNA and protein level in the sera of 133 men (82 tumorous and 51 healthy) and in cell lines derived from aggressive form of cancer. The level of these genes was determined and compared to prostatic specific antigen, widely used prostate cancer biomarker. We identified significantly (p < 0.05) decreased (> 4-fold) RNA level of Cav-1 NF-kB, c-FOS a c-JUN and significantly elevated (> 2-fold) RNA level of MT, AMACR, PSA, Ki-67, MMP-9 and ZIP1 and ZnT-1 (> 25-fold) in tumorous cell line 22Rv1 in comparison to healthy cell line PNT1A. On the protein level, we identified significant (> 20-fold) decrease of MT in cell lines. In contrary, serum MT level was significantly 4-fold increased. Furthermore, we identified insignificant changes in serum Cav-1 and AMACR. However, Cav-1 level was significantly increased in high stage TNM T4 patients and positively correlated with grading (r = 0.29 at p = 0.028). Thus, we may consider the combination of Cav-1 and MT as a high risk prostate cancer biomarker.
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