Expression of delayed rectifier potassium channels and their possible roles in proliferation of human gastric cancer cells
Expression of delayed rectifier potassium channels and their possible roles in proliferation of human gastric cancer cells
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DOI：
10.4161/cbt.4.12.2175
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发表时间：
2005-12-01
影响因子：
3.6
通讯作者：
Fan, DM
中科院分区：
文献类型：
--
作者：
Lan, M;Shi, YQ;Fan, DM
据报道，电压门控钾 (Kv) 通道参与多种类型细胞的增殖，包括肿瘤细胞。 Kv 通道的过度表达和相关通道活性参与肿瘤形成过程。我们前期的研究表明胃癌细胞SGC7901中存在延迟整流钾(I-K)电流。然而，大多数延迟整流钾（K-D）通道亚基在胃癌细胞中的表达和功能尚未完全解决。在这里，我们检测了永生化胃上皮细胞GES和各种胃癌细胞（包括AGS、KATOIII、MKN28、MKN45、MGC803、SGC7901、SGC7901/ADR和SGC7901/VCR）中Kv1-Kv3家族中K-D通道亚基的表达及其在细胞增殖中的作用。 RT-PCR 分析表明，所有检测的细胞系均表达 Kv1.3、Kv1.5、Kv1.6、Kv2.1 和 Kv2.2。然而，Kv1.2 和 Kv3.2 基因在任何给定的癌细胞系中几乎检测不到。 Kv1.5 蛋白在所有检查的细胞系中都有高 mRNA 水平，也在一些癌细胞系中表达，并且在胃癌组织中更常见。 RNA干扰下调SGC7901中Kv1.5的表达显着抑制SGC7901细胞的增殖和致瘤性。此外，在含Ca2+而不是不含Ca2+的培养基中，KCl (50mM)刺激空载体转染细胞中胞质钙浓度的快速增加，而维拉帕米可阻断该浓度。同样，用短干扰RNA降低Kv1.5的表达也阻止了去极化诱导的Ca2+流入。这一发现表明，多种胃癌细胞系中表达不止一种 KD 通道亚基。 Kv1.5可能通过控制Ca2+进入而参与肿瘤细胞增殖，干扰KD通道表达和/或活性可能为逆转胃癌细胞的恶性表型提供新策略。
Voltage-gated potassium (Kv) channels have been reported to be involved in the proliferation of many types of cells, including tumor cells. The overexpression of the Kv channels and related channel activity are involved in the neoplastic process. Our previous study has shown the existence of delayed rectifier potassium (I-K) current in gastric cancer cells SGC7901. However, the expression and function of most delayed rectifier potassium (K-D) channel subunits in gastric cancer cells are not completely resolved. Here we examine expression of K-D channel subunits in Kv1-Kv3 families in immortalized gastric epithelial cells GES and various gastric cancer cells (including AGS, KATOIII, MKN28, MKN45, MGC803, SGC7901, SGC7901/ADR and SGC7901/VCR), and their roles in cell proliferation. RT-PCR analysis reveals that all cell lines examined express Kv1.3, Kv1.5, Kv1.6, Kv2.1 and Kv2.2. However, Kv1.2 and Kv3.2 genes are barely detectable in any given cancer cell lines. Kv1.5 protein, high mRNA levels in all cell lines examined, is also expressed in some cancer cells lines and more frequently detected in gastric cancer tissues. Downregulation of the expression of Kv1.5 in SGC7901 with RNA interference significantly inhibited the proliferation and tumorigenicity of SGC7901 cells. Moreover, in Ca2+-containing rather than Ca2+-free medium, KCl (50mM) stimulated a rapid increase in the concentration of cytosolic calcium in empty vector transfected cells that was blocked by verapamil. Likewise, decrease the expression of Kv1.5 with short interfering RNA also blocked the depolarization-induced influx of Ca2+. This finding suggests that more than one kind of KD channel subunits are expressed in various gastric cancer cell lines. Kv1.5 may be involved in tumor cells proliferation by controlling Ca2+ entry, and the interference of KD channels expression and/or activity could provide a novel strategy to reverse the malignant phenotype of gastric cancer cells.