Role of KCNMA1 in breast cancer

Oeggerli, Martin; Tian, Yuemin; Ruiz, Christian; Wijker, Barbara; Sauter, Guido; Obermann, Ellen; Güth, Uwe; Zlobec, Inti; Sausbier, Matthias; Kunzelmann, Karl; Bubendorf, Lukas (2012). Role of KCNMA1 in breast cancer. PLoS ONE, 7(8), e41664. Lawrence, Kans.: Public Library of Science 10.1371/journal.pone.0041664

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KCNMA1 encodes the α-subunit of the large conductance, voltage and Ca(2+)-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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Zlobec, Inti

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:32

Last Modified:

26 Dec 2014 19:31

Publisher DOI:

10.1371/journal.pone.0041664

PubMed ID:

22899999

Web of Science ID:

000307380900014

BORIS DOI:

10.7892/boris.12498

URI:

https://boris.unibe.ch/id/eprint/12498 (FactScience: 218850)

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