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T‐type Ca 2+ Channel Expression in Human Esophageal Carcinomas: A Functional Role in Proliferation
Author(s) -
Chen Hairu,
Lu Fengmin,
Zhou Chun,
Guo Mingzhou,
Wu Songwei
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a538-a
Subject(s) - mibefradil , cell growth , cell culture , jurkat cells , patch clamp , microbiology and biotechnology , gene silencing , t type calcium channel , chemistry , cell type , biology , cell , cancer research , t cell , voltage dependent calcium channel , medicine , electrophysiology , immunology , receptor , biochemistry , gene , neuroscience , antagonist , genetics , immune system , calcium
In the present study, the role of T‐type Ca 2+ channels in cancer cell proliferation was examined. Eighteen 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 α 1 ‐subunits (α 1G , α 1H , and α 1I ) were detected in ten cell lines: α 1I was expressed either alone or in combination with α 1G and α 1H . These ten cell lines were then subjected to voltage‐clamp recordings; only one cell type (TE8) exhibited a typical T‐type current, whereas the others exhibited a minimal or no T‐type current. Cell proliferation assays were performed in the presence or absence of the T‐type channel blocker mibefradil in KYSE150 cells lacking expression of mRNA for T‐type channel α 1 ‐subunits, KYSE180 and TE1 cells expressing mRNA for T‐type channel α 1 ‐subunits but lacking T‐type current, and TE8 cells exhibiting T‐type current. Only TE8 cell proliferation was reduced by mibefradil. The reduction of cell proliferation in TE8 cells was found to be associated with an up‐regulation of p21 CIP1 . Moreover, p53 silencing nearly abolished the up‐regulation of p21 CIP1 resulting from mibefradil T‐type channel blockade. Together, these findings suggest a functional role of T‐type channels in certain esophageal carcinomas, and demonstrate that pharmacological inhibition of T‐type channels reduces cell proliferation via a p53‐dependent p21 CIP1 pathway. Supported by HL‐66299.