Role of KCNMA1 in Breast Cancer
Open Access
- 10 August 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (8), e41664
- https://doi.org/10.1371/journal.pone.0041664
Abstract
KCNMA1 encodes the α-subunit of the large conductance, voltage and Ca2+-activated (BK) potassium channel and has been reported as a target gene of genomic amplification at 10q22 in prostate cancer. To investigate the prevalence of the amplification in other human cancers, the copy number of KCNMA1 was analyzed by fluorescence-in-situ-hybridization (FISH) in 2,445 tumors across 118 different tumor types. Amplification of KCNMA1 was restricted to a small but distinct fraction of breast, ovarian and endometrial cancer with the highest prevalence in invasive ductal breast cancers and serous carcinoma of ovary and endometrium (3–7%). We performed an extensive analysis on breast cancer tissue microarrays (TMA) of 1,200 tumors linked to prognosis. KCNMA1 amplification was significantly associated with high tumor stage, high grade, high tumor cell proliferation, and poor prognosis. Immunofluorescence revealed moderate or strong KCNMA1 protein expression in 8 out of 9 human breast cancers and in the breast cancer cell line MFM223. KCNMA1-function in breast cancer cell lines was confirmed by whole-cell patch clamp recordings and proliferation assays, using siRNA-knockdown, BK channel activators such as 17ß-estradiol and the BK-channel blocker paxilline. Our findings revealed that enhanced expression of KCNMA1 correlates with and contributes to high proliferation rate and malignancy of breast cancer.Keywords
This publication has 40 references indexed in Scilit:
- Enhancement of BKCa channel activity induced by hydrogen peroxide: Involvement of lipid phosphatase activity of PTENBiochimica et Biophysica Acta (BBA) - Biomembranes, 2009
- Modulation of BKCaChannel Gating by Endogenous Signaling MoleculesPhysiology, 2009
- Direct Regulation of BK Channels by Phosphatidylinositol 4,5-Bisphosphate as a Novel Signaling PathwayThe Journal of general physiology, 2008
- K+ Channel Expression in Human Breast Cancer Cells: Involvement in Cell Cycle Regulation and CarcinogenesisThe Journal of Membrane Biology, 2007
- High-conductance potassium channels of the SLO familyNature Reviews Neuroscience, 2006
- BK Ca -Cav Channel Complexes Mediate Rapid and Localized Ca 2+ -Activated K + SignalingScience, 2006
- Large conductance Ca2+-activated K+ (BK) channel: Activation by Ca2+ and voltageBiological Research, 2006
- Ion Channels and CancerThe Journal of Membrane Biology, 2005
- Functional and molecular identification of intermediate-conductance Ca2+-activated K+channels in breast cancer cells: association with cell cycle progressionAmerican Journal of Physiology-Cell Physiology, 2004
- Slo1 Tail Domains, but Not the Ca2+ Bowl, Are Required for the β1 Subunit to Increase the Apparent Ca2+ Sensitivity of BK ChannelsThe Journal of general physiology, 2002