Involvement of TRPC channels in lung cancer cell differentiation and the correlation analysis in human non-small cell lung cancer.
Involvement of TRPC channels in lung cancer cell differentiation and the correlation analysis in human non-small cell lung cancer.
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DOI：
10.1371/journal.pone.0067637
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Xu SZ
中科院分区：
文献类型：
--
作者：
Jiang HN;Zeng B;Zhang Y;Daskoulidou N;Fan H;Qu JM;Xu SZ
经典瞬时受体电位（TRPC）通道是一种Ca ~（2+）可透过的阳离子通道，通过G蛋白偶联受体激活和/或Ca ~（2+）库耗竭来控制Ca ~（2+）内流。在这里，我们调查TRPC参与肺癌细胞分化。应用实时荧光定量PCR和免疫组化技术，检测28例非小细胞肺癌（NSCLC）组织中TRPC的表达，并分析其与NSCLC分化程度的关系。用PCR和Western blotting检测肺癌细胞株A549中TRPCs的表达与细胞分化的关系。用全反式维甲酸（ATRA）处理后，用钙离子成像和膜片记录法检测通道活性。TRPC 1、3、4、6的表达与NSCLC的分化程度有关，而与年龄、性别、吸烟史、肺癌细胞类型无关。ATRA可上调A549细胞TRPC 3、TRPC 4和TRPC 6的表达，增加细胞内Ca ~（2+）内流，但对TRPC通道无直接影响。TRPC通道的孔封闭抗体抑制细胞有丝分裂减少，这是抵消了慢性治疗与全反式维甲酸。阻断TRPC通道可抑制A549细胞增殖，而过表达TRPC可促进A549细胞增殖。我们的结论是TRPC表达与肺癌分化相关。TRPCs介导ATRA的药理作用，在调节肺癌细胞的分化和增殖中发挥重要作用，这为肺癌生物学和潜在的抗癌治疗提供了新的认识。
The canonical transient receptor potential (TRPC) channels are Ca2+-permeable cationic channels controlling the Ca2+ influx evoked by G protein-coupled receptor activation and/or by Ca2+ 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 Ca2+ 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 Ca2+ 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.
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影响因子：
5.8
作者：
Jiang, Hongni;Zeng, Bo;Xu, Shang-Zhong
通讯作者：
Xu, Shang-Zhong
影响因子：
3.8
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11.2
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168.9
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通讯作者：
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3.2
作者：
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通讯作者：
Atkin, Stephen L.