Oeggerli, Martin and Tian, Yuemin and Ruiz, Christian and Wijker, Barbara and Sauter, Guido and Obermann, Ellen and Gueth, Uwe and Zlobec, Inti and Sausbier, Matthias and Kunzelmann, Karl and Bubendorf, Lukas (2012) Role of KCNMA1 in Breast Cancer. PLOS ONE, 7 (8): e41664. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
KCNMA1 encodes the a-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 17 beta-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: | Article |
|---|---|
| Uncontrolled Keywords: | CA2+-ACTIVATED K+ CHANNELS; ION CHANNELS; POTASSIUM CHANNELS; ANDROGEN RECEPTOR; BK CHANNEL; TISSUE MICROARRAYS; CELL-PROLIFERATION; EXPRESSION; GENE; ACTIVATION; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 May 2020 06:38 |
| Last Modified: | 07 May 2020 06:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18302 |
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