121 LOSS OF TRANSGLUTAMINASE 2 (TG2) ACTIVITY PROMOTES RENAL CELL CARCINOMA (RCC)

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research1 Apr 2011121 LOSS OF TRANSGLUTAMINASE 2 (TG2) ACTIVITY PROMOTES RENAL CELL CARCINOMA (RCC) Merve Erdem, Selcuk Erdem, Oner Sanli, Fikrettin Sahin, Isin Kilicarslan, and Dilek Telci Merve ErdemMerve Erdem Istanbul, Turkey More articles by this author , Selcuk ErdemSelcuk Erdem Istanbul, Turkey More articles by this author , Oner SanliOner Sanli Istanbul, Turkey More articles by this author , Fikrettin SahinFikrettin Sahin Istanbul, Turkey More articles by this author , Isin KilicarslanIsin Kilicarslan Istanbul, Turkey More articles by this author , and Dilek TelciDilek Telci Istanbul, Turkey More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.187AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES TG2 is a multifunctional enzyme that can decrease the migratory ability of cancer cells when secreted into the extracellular (EC) space through cross-linking the EC matrix proteins which then become resistant against the proteolytic degradation. Primary tumors of the liver, breast, and skin show reduced TG2 expression and activity in the tumor body resulting in progression of the primary tumor. However, increased TG2 expression in parallel with the integrin β1 (ITGB1) was detected in tumors isolated from metastatic sites. We previously showed that interaction of TG2 with syndecan-4 (SDC-4) and ITGB1 results in the loss of enzyme activity and promotes cell survival. Hence, the objective of this study was to investigate the importance of TG2 along with SDC-4 and ITGB1 in RCC progression. METHODS The expression level of TG2, ITGB1, and SDC-4 in the primary RCC cell line A-498 and control RPTEC (primary renal proximal tubule epithelial) cell line along with healthy and tumor tissue samples from 62 patients with RCC was evaluated by real time-PCR. TG2 activity in randomly selected patient samples and cell lines was measured by transamidation activity assay. RESULTS TG2 expression ratio showed a significant 2.3 fold decrease in A-498 cells when compared with the control RPTEC. A 3 fold decrease in TG2 expression levels were recorded in the 65% of primary RCC (P < 0.0001) regardless of the grade of the tumor. Rest of the tumors showed a 2.1 fold increase in the TG2 expression ratio, which was found to be in parallel with the increase in ITGB1 and SDC-4 expression levels in 87% of the cases. A-498 cells contained 2 fold less TG2 activity compared to RPTECs, while a remarkable decrease in TG2 activity was seen both in tumors with reduced TG2 expression and in tumors with a high TG2 expression in parallel with high ITGB1 and SDC4. CONCLUSIONS There was a statistically significant decrease in the expression and activity of TG2 in RCC cell line and tumors suggesting that the loss of the TG2 activity promotes RCC possibly through rendering the ECM more susceptible to proteolytic degradation. A subpopulation of RCC tumors showed increased TG2 expression but not activity in conjunction with increased ITGB1 and SDC4 expression where TG2 may be acting as a cell adhesion protein affecting the cell migration and survival. Whether increased TG2 expression in association with the ITGB1 and SDC4 expression predisposed this subpopulation of patients to metastasis will be determined with the patient follow-up in the future studies. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e51 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Merve Erdem Istanbul, Turkey More articles by this author Selcuk Erdem Istanbul, Turkey More articles by this author Oner Sanli Istanbul, Turkey More articles by this author Fikrettin Sahin Istanbul, Turkey More articles by this author Isin Kilicarslan Istanbul, Turkey More articles by this author Dilek Telci Istanbul, Turkey More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...