TRPV2 channel negatively controls glioma cell proliferation and resistance to Fas-induced apoptosis in ERK-dependent manner

Abstract

The aim of this study was to investigate the expression and function of the transient receptor potential vanilloid 2 (TRPV2) in human glioma cells. By Real-Time-PCR and western blot analysis, we found that TRPV2 messenger RNA (mRNA) and protein were expressed in benign astrocyte tissues, and its expression progressively declined in high-grade glioma tissues as histological grade increased (n = 49 cases), and in U87MG cells and in MZC, FCL and FSL primary glioma cells. To investigate the function of TRPV2 in glioma, small RNA interfering was used to silence TRPV2 expression in U87MG cells. As evaluated by RT-Profiler PCR array, siTRPV2-U87MG transfected cells displayed a marked downregulation of Fas and procaspase-8 mRNA expression, associated with upregulation of cyclin E1, cyclin-dependent kinase 2, E2F1 transcriptor factor 1, V-raf-1 murine leukemia viral oncogene homolog 1 and Bcl-2-associated X protein (Bcl-X(L)) mRNA expression. TRPV2 silencing increased U87MG cell proliferation as shown by the increased percentage of cells incorporating 5-bromo-2-deoxyuridine expressing beta(III)-tubulin and rescued glioma cells to Fas-induced apoptosis. These events were dependent on extracellular signal-regulated kinase (ERK) activation: indeed inhibition of ERK activation in siTRPV2-U87MG transfected cells by treatment with PD98059, a specific mitogen-activated protein kinase/extracellular signal-regulated kinase kinase inhibitor, reduced Bcl-X(L) protein levels, promoted Fas expression, and restored Akt/protein kinase B pathway activation leading to reduced U87MG cell survival and proliferation, and increased sensitivity to Fas-induced apoptosis. In addition, transfection of TRPV2 in MZC glioma cells, by inducing Fas overexpression, resulted in a reduced viability and an increased spontaneous and Fas-induced apoptosis. Overall, our findings indicate that TRPV2 negatively controls glioma cell survival and proliferation, as well as resistance to Fas-induced apoptotic cell death in an ERK-dependent manner.

Transient receptor potential (TRP) channels, promising potential diagnostic and therapeutic tools for cancer

“…TRPV2 negatively controls glioma cell survival and proliferation and protects the cells from Fas-induced apoptosis in an ERK-dependent manner (75,76).…”

“…The most interesting finding is that exposure to menthol drastically reduced the survival of melanoma cells (84). TRPV2 mRNA is found in benign astrocyte tissues, and its expression progressively decreased in high-grade glioma tissues as the histological grade increased (76).…”

Ionic Channels in the Therapy of Malignant Glioma

“…Down-regulation of TRPV2 by RNA interference actually promoted U87MG glioma cell proliferation and rescued Fasinduced cell apoptosis. On the contrary, overexpression of TRPV2 in MZC glioma cells resulted in reduced cell viability and increased spontaneous and Fas-induced apoptosis (Nabissi et al, 2010).…”

TRPV2 (transient receptor potential cation channel, subfamily V, member 2)

“…Disease TRPV2 channel is expressed in glioma cells: U87MG, MZC, FCL and FSL primary human glioma cells (Nabissi et al, 2010). Prognosis The findings indicate that TRPV2 negatively controls glioma cell survival and proliferation.…”

“…TRPV2 is expressed in the human larynx, which may act as laryngeal nociceptors perceiving luminal noxious stimuli. TRPV2 mRNA and protein are expressed in benign astrocyte tissues, and its expression progressively declined in high-grade glioma tissues as histological grade increased (n = 49 cases), and in U87MG cells and in MZC, FCL and FSL primary glioma cells (Nabissi et al, 2010).…”