KCNMA1 gene amplification promotes tumor cell proliferation in human prostate cancer.
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KCNMA1 gene amplification promotes tumor cell proliferation in human prostate cancer. / Bloch, M; Ousingsawat, J; Simon, Ronald; Schraml, P; Gasser, T C; Mihatsch, M J; Kunzelmann, K; Bubendorf, L.
In: ONCOGENE, Vol. 26, No. 17, 17, 2007, p. 2525-2534.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - KCNMA1 gene amplification promotes tumor cell proliferation in human prostate cancer.
AU - Bloch, M
AU - Ousingsawat, J
AU - Simon, Ronald
AU - Schraml, P
AU - Gasser, T C
AU - Mihatsch, M J
AU - Kunzelmann, K
AU - Bubendorf, L
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 26
SP - 2525
EP - 2534
JO - ONCOGENE
JF - ONCOGENE
SN - 0950-9232
IS - 17
M1 - 17
ER -