Department of Pulmonary Medicine, Zhongshan Hospital, School of Medicine, Fudan University, Shanghai, China.
PLoS One. 2013 Jun 28;8(6):e67637. doi: 10.1371/journal.pone.0067637. Print 2013.
The canonical transient receptor potential (TRPC) channels are Ca(2+)-permeable cationic channels controlling the Ca(2+) influx evoked by G protein-coupled receptor activation and/or by Ca(2+) store depletion. Here we investigate the involvement of TRPCs in the cell differentiation of lung cancer. The expression of TRPCs and the correlation to cancer differentiation grade in non-small cell lung cancer (NSCLC) were analyzed by real-time PCR and immunostaining using tissue microarrays from 28 patient lung cancer samples. The association of TRPCs with cell differentiation was also investigated in the lung cancer cell line A549 by PCR and Western blotting. The channel activity was monitored by Ca(2+) imaging and patch recording after treatment with all-trans-retinoic acid (ATRA). The expression of TRPC1, 3, 4 and 6 was correlated to the differentiation grade of NSCLC in patients, but there was no correlation to age, sex, smoking history and lung cancer cell type. ATRA upregulated TRPC3, TRPC4 and TRPC6 expression and enhanced Ca(2+) influx in A549 cells, however, ATRA showed no direct effect on TRPC channels. Inhibition of TRPC channels by pore-blocking antibodies decreased the cell mitosis, which was counteracted by chronic treatment with ATRA. Blockade of TRPC channels inhibited A549 cell proliferation, while overexpression of TRPCs increased the proliferation. We conclude that TRPC expression correlates to lung cancer differentiation. TRPCs mediate the pharmacological effect of ATRA and play important roles in regulating lung cancer cell differentiation and proliferation, which gives a new understanding of lung cancer biology and potential anti-cancer therapy.
经典的瞬时受体电位（TRPC）通道是钙离子通透的阳离子通道，控制 G 蛋白偶联受体激活和/或钙储存耗竭引起的钙离子内流。在这里，我们研究了 TRPC 通道在肺癌细胞分化中的作用。通过实时 PCR 和免疫组化分析，使用来自 28 例非小细胞肺癌（NSCLC）患者的组织微阵列，分析了 TRPCs 的表达及其与癌症分化程度的相关性。通过 PCR 和 Western blot，在肺癌细胞系 A549 中还研究了 TRPCs 与细胞分化的相关性。用全反式视黄酸（ATRA）处理后，通过钙离子成像和膜片钳记录监测通道活性。TRPC1、3、4 和 6 的表达与患者 NSCLC 的分化程度相关，但与年龄、性别、吸烟史和肺癌细胞类型无关。ATRA 上调了 TRPC3、TRPC4 和 TRPC6 的表达并增强了 A549 细胞中的钙离子内流，但是 ATRA 对 TRPC 通道没有直接作用。TRPC 通道的阻断剂通过孔阻断抗体减少了细胞有丝分裂，而慢性 ATRA 处理则逆转了这一作用。阻断 TRPC 通道抑制了 A549 细胞的增殖，而过表达 TRPC 则增加了增殖。我们得出结论，TRPC 的表达与肺癌的分化有关。TRPC 介导 ATRA 的药理作用，并在调节肺癌细胞分化和增殖方面发挥重要作用，这为肺癌生物学和潜在的抗癌治疗提供了新的认识。
