Oncogenic potential of TASK3 (Kcnk9) depends on K+ channel function

Pei, L., Wiser, O., Slavin, A., Mu, D., Powers, S., Jan, L. Y., Hoey, T. (June 2003) Oncogenic potential of TASK3 (Kcnk9) depends on K+ channel function. Proceedings of the National Academy of Sciences of the United States of America, 100 (13). pp. 7803-7. ISSN 0027-8424

URL: http://www.ncbi.nlm.nih.gov/pubmed/12782791
DOI: 10.1073/pnas.1232448100

Abstract

TASK3 gene (Kcnk9) is amplified and overexpressed in several types of human carcinomas. In this report, we demonstrate that a point mutation (G95E) within the consensus K+ filter of TASK3 not only abolished TASK3 potassium channel activity but also abrogated its oncogenic functions, including proliferation in low serum, resistance to apoptosis, and promotion of tumor growth. Furthermore, we provide evidence that TASK3G95E is a dominant-negative mutation, because coexpression of the wild-type and the mutant TASK3 resulted in inhibition of K+ current of wild-type TASK3 and its tumorigenicity in nude mice. These results establish a direct link between the potassium channel activity of TASK3 and its oncogenic functions and imply that blockers for this potassium channel may have therapeutic potential for the treatment of cancers.

Item Type: Paper
Uncontrolled Keywords: Animals Apoptosis Cell Division Cell Line Cells, Cultured Electrophysiology Fibroblasts/metabolism Membrane Potentials Mice Mice, Nude Microscopy, Fluorescence Mutagenesis, Site-Directed Mutation Neoplasms/*etiology Plasmids/metabolism Point Mutation Potassium Channels/genetics/*metabolism/*physiology *Potassium Channels, Tandem Pore Domain RNA, Complementary/metabolism Time Factors Transfection Xenopus
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell division
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene
CSHL Authors:
Communities: CSHL labs > Powers lab
Depositing User: Matt Covey
Date: 24 June 2003
Date Deposited: 25 Feb 2014 16:22
Last Modified: 25 Feb 2014 16:22
PMCID: PMC164668
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29533

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