TRPM2 mediates distruption of autophagy machinery and correlates with the grade level in prostate cancer.

Autor: Tektemur A; Department of Medical Biology, Faculty of Medicine, Firat University, Elazig, Turkey. atektemur@firat.edu.tr., Ozaydin S; Department of Medical Biology, Faculty of Medicine, Firat University, Elazig, Turkey., Etem Onalan E; Department of Medical Biology, Faculty of Medicine, Firat University, Elazig, Turkey., Kaya N; Department of Histology, Faculty of Medicine, Firat University, Elazig, Turkey., Kuloglu T; Department of Histology, Faculty of Medicine, Firat University, Elazig, Turkey., Ozercan İH; Department of Medical Pathology, Faculty of Medicine, Firat University, Elazig, Turkey., Tekin S; Department of Physiology, Faculty of Medicine, Inonu University, Malatya, Turkey., Elyas HM; Department of Medical Biology, Faculty of Medicine, Firat University, Elazig, Turkey.
Jazyk: angličtina
Zdroj: Journal of cancer research and clinical oncology [J Cancer Res Clin Oncol] 2019 May; Vol. 145 (5), pp. 1297-1311. Date of Electronic Publication: 2019 Mar 19.
DOI: 10.1007/s00432-019-02898-z
Abstrakt: Purpose: Transient receptor potential melastatin 2 (TRPM2), a calcium-permeable ion channel, is shown as a prognostic marker candidate in prostate cancer (PCa) and an important regulator of autophagy. We aimed to determine the changes in TRPM2 and autophagic-apoptotic gene expression levels in human prostate adenocarcinomas, and to investigate the affect of TRPM2 on autophagic pathways in PC-3 cell line.
Methods: Human prostate tissues were classified considering the grade levels and were divided into the control, BPH, and grade 1-5 groups. mRNA expression levels of genes were determined by qPCR. In addition, TRPM2 was evaluated immunohistochemically for each group. In PC-3 cell line, TRPM2 was silenced through siRNA transfection, and autophagy induction was analyzed by acridine orange (AO) staining.
Results: The qPCR and immunoreactivity results showed that the increased TRPM2 expression levels in human PCa samples were paralleled with higher grade levels. The autophagic-apoptotic gene expressions showed high variability in different grade levels. Also, silencing TRPM2 in PC-3 cells altered autophagic gene expressions and caused autophagy induction according to the AO staining results.
Conclusion: We showed that the autophagy-TRPM2 association may take place in the molecular basis of PCa and accordingly this connection may be targeted as a new therapeutic approach in PCa.
Databáze: MEDLINE
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