Novel role for the transient receptor potential channel TRPM2 in prostate cancer cell proliferation.

Novel role for the transient receptor potential channel TRPM2 in prostate cancer cell proliferation.
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DOI:
10.1038/pcan.2009.55
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发表时间:
2010-06
影响因子:
4.8
通讯作者:
Li, M.
Li, M.
中科院分区:
医学2区
文献类型:
--
作者:
Zeng, X.;Sikka, S. C.;Huang, L.;Sun, C.;Xu, C.;Jia, D.;Abdel-Mageed, A. B.;Pottle, J. E.;Taylor, J. T.;Li, M.

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我们已经确定了瞬时受体电位(TRP)蛋白超家族成员TRPM 2在前列腺癌细胞增殖中的新功能。TRPM 2编码非选择性阳离子可渗透离子通道。我们发现用小干扰RNA技术选择性地敲低TRPM 2抑制前列腺癌细胞的生长,但不抑制非癌细胞的生长。这种蛋白质的亚细胞定位在癌细胞和非癌细胞之间也是显著不同的。在BPH-1(良性)中,TRPM 2蛋白均匀地位于质膜附近和细胞质中,而在癌细胞(PC-3和DU-145)中,大量的TRPM 2蛋白以成簇模式位于细胞核中。此外,我们发现TRPM 2抑制前列腺癌细胞核ADP-核糖基化。然而,TRPM 2敲低诱导的增殖抑制是独立的聚(ADP-核糖)聚合酶的活性。我们的结论是,TRPM 2是必不可少的前列腺癌细胞增殖,并可能是一个潜在的目标,为前列腺癌的选择性治疗。
We have identified a novel function for a member of the transient receptor potential (TRP) protein super-family, TRPM2, in prostate cancer cell proliferation. TRPM2 encodes a non-selective cation-permeable ion channel. We found that selectively knocking down TRPM2 with the small interfering RNA technique inhibited the growth of prostate cancer cells but not of non-cancerous cells. The subcellular localization of this protein is also remarkably different between cancerous and non-cancerous cells. In BPH-1 (benign), TRPM2 protein is homogenously located near the plasma membrane and in the cytoplasm, whereas in the cancerous cells (PC-3 and DU-145), a significant amount of the TRPM2 protein is located in the nuclei in a clustered pattern. Furthermore, we have found that TRPM2 inhibited nuclear ADP-ribosylation in prostate cancer cells. However, TRPM2 knockdown-induced inhibition of proliferation is independent of the activity of poly(ADP-ribose) polymerases. We conclude that TRPM2 is essential for prostate cancer cell proliferation and may be a potential target for the selective treatment of prostate cancer.
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