Tumor necrosis factor a accelerates Hep-2 cells proliferation by suppressing TRPP2 expression

TRPP2, a Ca^(2+)-permeable non-selective cation channel, has been shown to negatively regulate cell cycle, but the mechanism underlying this regulation is unknown. Tumor necrosis factor a(TNF-α) is a proinflammatory cytokine extensively involved in immune system regulation, cell proliferation and cell survival. However, the effects and mechanisms for the role of TNF-αin laryngeal cancer remain unclear. Here, we demonstrated using western blot analyses and intracellular Ca^(2+) concentration measurements that TNF-α treatment suppressed both TRPP2 expression and ATP-induced Ca^(2+) release in a laryngeal cancer cell line(Hep-2). Knockdown of TRPP2 by a specific siRNA significantly decreased ATP-induced Ca^(2+) release and abolished the effect of TNF-α on the ATP-induced Ca^(2+) release. TNF-α treatment also enhanced Hep-2 cell proliferation and growth, as determined using cell counting and flow cytometry cell cycle assays. Moreover, TNF-α treatment down-regulated phosphorylated protein kinase R-like endoplasmic reticulum kinase(p-PERK) and phosphorylated eukaryotic translation initiation factor(p-eIF2α)expression levels, without affecting PERK and eIF2 a expression levels in Hep-2 cells. We concluded that suppressing TRPP2 expression and TRPP2-mediated Ca^(2+) signaling may be one mechanism underlying TNF-α-enhanced Hep-2 cell proliferation.These results offer new insights into the mechanisms of TNF-α-mediated laryngeal cancer cell proliferation, and provide evidences showing a potential role of TNF-α in the development of laryngeal cancer.

TRPP2, a Ca2＋-permeable non-selective cation channel, has been shown to negatively regulate cell cycle, but the mechanism underlying this regulation is unknown. Tumor necrosis factor a （TNF-a） is a proinflammatory cytokine extensively involved in immune system regulation, cell proliferation and cell survival. However, the effects and mechanisms for the role of TNF-a in laryngeal cancer remain unclear. Here, we demonstrated using western blot analyses and intracellular Ca〉 concentration measurements that TNF-a treatment suppressed both TRPP2 expression and ATP-induced Ca2＋ release in a laryngeal cancer cell line （Hep-2）. Knockdown of TRPP2 by a specific siRNA significantly decreased ATP-induced Ca2＋ release and abolished the effect of TNF-a on the ATP-induced Ca2＋ release. TNF-a treatment also enhanced Hep-2 cell proliferation and growth, as determined using cell counting and flow cytometry cell cycle assays. Moreover, TNF-a treatment down-regulated phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK） and phosphorylated eukaryotic translation initiation factor （p-elF2c0 expression levels, without affecting PERK and elF2ct expression levels in Hep-2 cells. We concluded that suppressing TRPP2 expression and TRPP2-mediated Ca2＋ signaling may be one mechanism underlying TNF〈t-enhanced Hep-2 cell proliferation. These results offer new insights into the mechanisms of TNF-a-mediated laryngeal cancer cell proliferation, and provide evidences showing a potential role of TNF-a in the development of laryngeal cancer.