Metallothionein – zinc – prostate cancer: pathogenesis and diagnostic use

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Authors

GUMULEC Jaromír CERNEI Natalia Vladimirovna ZÍTKA Ondřej MASAŘÍK Michal BABULA Petr ADAM Vojtěch KIZEK René

Year of publication 2010
Type Article in Proceedings
Conference MendelNet 2010
MU Faculty or unit

Faculty of Medicine

Citation
Web http://www.af.mendelu.cz/mendelnet
Field Oncology and hematology
Keywords metallothionein;zinc;prostate cancer;magnetic particles;PC-3;PNT1A;tumor marker
Description Prostate cancer (PCa) is one of the most frequent cancer and one of the most frequent cancer-related cause of death among men. Therefore, early diagnosis, differentiation between risky and relative benign forms and understanding of pathogenesis of disease for further therapeutic approaches is highly desirable. Healthy prostate is unique in zinc accumulation. Zinc is (mostly) buffered by cysteine-rich low molecular protein metallothionein (MT). In contrast, PCa has altered zinc metabolism and elevated MT. In PCa patients, MT is elevated even in serum and can therefore be used as potential tumor marker due to high specifity to PCa. This could be very desirable because of inaccuracies of current prostatic specific antigen (PSA) screening. The aims of this study is (1) to analyze MT-zinc relation on cell lines: to determine zinc and MT levels in cell lines PC-3 (cancer) and PNT1A (control), (2) to find relations between MT and PSA, (3) to describe potential effects of MT and/or zinc on prostate cancer pathogenesis, (4) to determine serum MT level,(5) to find relations between MT level and patient’s disease grading. We used (1) optimized fully automated immunochemical methods for detection of serum PSA in serum, (2) protein separation with paramagnetic microparticles modified with antibody against PSA and MT, (3) PAGE gel silver and coomassie staining and colorimetric detection. We found (1) statistically significant (p=0,001) MT elevation in PCa lines and in PCa serum, (2) significant PSA elevation in cell lines, (3) strong correlation between intracel. zinc and MT, (4) no correlation between disease grading/patient’s history, PSA level and MT level. We found MT/zinc play a role in PCa pathogenesis, further understanding may have therapeutic implications. By our findings, MT is a good candidate for new marker for PCa screening, developing of automated diagnostic methods is highly desirable.
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