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Transient Receptor Potential Melastatin 7–like Current in Human Head and Neck Carcinoma Cells: Role in Cell Proliferation

¹ ENT Department, Guangdong Provincial People's Hospital; ² ENT Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China; and ³ Robert S. Dow Neurobiology Laboratories, Legacy Research, Portland, Oregon

Requests for reprints: Zhigang Xiong, Robert S. Dow Neurobiology Laboratories, Legacy Research, 1225 Northeast 2nd Avenue, Portland, OR 97232. Phone: 503-413-2086; E-mail: zxiong{at}Downeurobiology.org.

Ion channels are involved in normal physiologic processes and in the pathology of various diseases. In this study, we investigated the presence and potential function of transient receptor potential melastatin 7 (TRPM7) channels in the growth and proliferation of FaDu and SCC25 cells, two common human head and neck squamous carcinoma cell lines, using a combination of patch-clamp recording, Western blotting, immunocytochemistry, small interfering RNA (siRNA), fluorescent Ca²⁺ imaging, and cell counting techniques. Although voltage-gated K⁺ currents were recorded in all cells, none of FaDu cells express voltage-gated Na⁺ or Ca²⁺ currents. Perfusion of cells with NMDA or acidic solution did not activate inward currents, indicating a lack of NMDA receptor and acid-sensing channels. Lowering extracellular Ca²⁺, however, induced a large nondesensitizing current reminiscent of Ca²⁺-sensing cation current or TRPM7 current previously described in other cells. This Ca²⁺-sensing current can be inhibited by Gd³⁺, 2-aminoethoxydiphenyl borate (2-APB), or intracellular Mg²⁺, consistent with the TRPM7 current being activated. Immunocytochemistry, Western blot, and reverse transcription-PCR detected the expression of TRPM7 protein and mRNA in these cells. Transfection of FaDu cells with TRPM7 siRNA significantly reduced the expression of TRPM7 mRNA and protein as well as the amplitude of the Ca²⁺-sensing current. Furthermore, we found that Ca²⁺ is critical for the growth and proliferation of FaDu cells. Blockade of TRPM7 channels by Gd³⁺ and 2-APB or suppression of TRPM7 expression by siRNA inhibited the growth and proliferation of these cells. Similar to FaDu cells, SCC25 cells also express TRPM7-like channels. Suppressing the function of these channels inhibited the proliferation of SCC25 cells. [Cancer Res 2007;67(22):10929–38]

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