T-type Ca2+ channel expression in human esophageal carcinomas:: A functional role in proliferation
T-type Ca2+ channel expression in human esophageal carcinomas:: A functional role in proliferation
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DOI：
10.1016/j.ceca.2007.03.006
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发表时间：
2008-01-01
期刊：
影响因子：
4
通讯作者：
Wu, Songwei
中科院分区：
文献类型：
--
作者：
Lu, Fengmin;Chen, Hairu;Wu, Songwei
本研究探讨了T型钙通道在癌细胞增殖中的作用。用RT-PCR和电压钳记录技术对17株人食道癌细胞株进行了T型通道的筛选。在所有17个细胞系中检测到所有三个T型通道α(1)亚单位(α(IG)、α(IH)和α(II))的mRNAs：单独的α(1H)、α(IH)和α(IG)，或所有三个T型α(I)亚单位。11个细胞系进一步接受电压钳记录：一个，即TE8细胞系，被发现表现出典型的T型电流，而其他细胞系表现出最小的或没有T型电流。在KYSE150、KYSE 180和表达T型通道α(1)亚单位的T型通道α(1)亚单位mRNA的TE1细胞中，有或没有T型通道阻断剂mibefradil的情况下进行细胞增殖分析11个细胞株进一步进行电压钳记录：一个细胞系，即TE8细胞系，显示出典型的T型电流，而其他细胞株显示出极小的T型电流或不显示T型电流。在KYSE150、KYSE180和TEI细胞表达T型通道α(1)亚单位但缺乏T型电流的KYSE150、KYSE180和TEI细胞以及表现T型电流的TE8细胞在有或没有T型通道阻断剂mibefradil的情况下进行细胞增殖分析。米贝拉地尔仅抑制TE8细胞的增殖。通过类型特异性shRNA转导沉默TE8细胞中编码功能性T-型钙通道的α(IG)基因也显著降低了TE8细胞的增殖。研究发现，TE8细胞增殖抑制与p21(Cipi)表达上调有关。此外，P53的沉默几乎取消了米贝拉地尔T型通道阻断引起的p21(Cipi)的上调。综上所述，这些发现提示T型通道在某些食道癌中起功能作用，抑制T型通道通过P53依赖的p21(CIPI)途径减少细胞增殖。(C)2007爱思唯尔有限公司。保留所有权利。
In the present study the role of T-type Ca2+ channels in cancer cell proliferation was examined. Seventeen human esophageal cancer cell lines were screened for T-type channels using RT-PCR and voltage-clamp recordings. mRNAs for all three T-type channel alpha(1)-subunits (alpha(IG), alpha(IH), and alpha(II)) were detected in all 17 cell lines: either alpha(1H) alone, alpha(IH) and alpha(IG), or all three T-type alpha(I)-subunits. Eleven cell lines were further subjected to voltage-clamp recordings: one, i.e. the TE8 cell line, was found to exhibit a typical T-type current while others exhibited a minimal or no T-type current. Cell proliferation assays were performed in the presence or absence of T-type channel blocker mibefradil in KYSE150, KYSE 180 and TE 1 cells expressing mRNA for T-type channel alpha(1)-subunits Eleven cell lines were further subjected to voltage-clamp recordings: one, i.e. the TE8 cell line, was found to exhibit a typical T-type current while others exhibited a minimal or no T-type current. Cell proliferation assays were performed in the presence or absence of T-type channel blocker mibefradil in KYSE150, KYSE180 and TEI cells expressing mRNA for T-type channel alpha(1)-subunits but lacking T-type current, and TE8 cells exhibiting T-type current. Only TE8 cell proliferation was reduced by mibefradil. Silencing the alpha(IG)-gene that encodes functional T-type Ca2+ channels in TE8 cells with type-specific shRNA transduction also significantly decreased TE8 cell proliferation. The reduction of cell proliferation in TE8 cells was found to be associated with an up-regulation of p21(CIPI). Moreover, p53 silencing nearly abolished the up-regulation of p21(CIPI) resulting from mibefradil T-type channel blockade. Together, these findings suggest a functional role of T-type channels in certain esophageal carcinomas, and that inhibition of T-type channels reduces cell proliferation via a p53-dependent p21(CIPI) pathway. (c) 2007 Elsevier Ltd. All rights reserved.