Bloch, M. and Ousingsawat, J. and Simon, R. and Schraml, P. and Gasser, T. C. and Mihatsch, M. J. and Kunzelmann, K. and Bubendorf, L. (2007) KCNMA1 gene amplification promotes tumor cell proliferation in human prostate cancer. ONCOGENE, 26 (17). pp. 2525-2534. ISSN 0950-9232,
Full text not available from this repository. (Request a copy)Abstract
Molecular mechanisms of prostate cancer progression are poorly understood. Here, we studied gene amplification of the large conductance calcium-activated potassium channel alpha subunit (KCNMA1), which is located at the chromosomal region 10q22. Fluorescence in situ hybridization ( FISH) revealed KCNMA1 amplification in 16% of 119 late-stage human prostate cancers and in the hormone-insensitive prostate cancer cell line PC-3. In contrast, KCNMA1 amplification was absent in 33 benign controls, 32 precursor lesions and in 105 clinically organ-confined prostate cancers. Amplification was associated with mRNA and protein overexpression as well as increased density of BK channel protein and beta-estradiol-insensitive BK currents in PC-3 cells as compared to non-amplified control cell lines. Specific blockade of BK channels by iberiotoxin or RNA(i) significantly inhibited K+ currents and growth of PC-3 cells. The data demonstrate that 10q22 amplification drives KCNMA1 expression and cell proliferation. Thus, KCNMA1 qualifies as a promising diagnostic and therapeutic target in patients with prostate cancer.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COMPARATIVE GENOMIC HYBRIDIZATION; ACTIVATED POTASSIUM CHANNELS; MAXI-K CHANNELS; LARGE-CONDUCTANCE; EPITHELIAL-CELLS; UROKINASE GENE; BREAST-CANCER; BK CHANNELS; RECEPTOR; KINASE; prostate cancer; progression; amplification; BK channel; KCNMA1 |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2020 13:28 |
| Last Modified: | 14 Dec 2020 13:28 |
| URI: | https://pred.uni-regensburg.de/id/eprint/32890 |
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