Role of KCNMA1 in breast cancer.
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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.
in: PLOS ONE, Jahrgang 7, Nr. 8, 8, 2012, S. 41664.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Role of KCNMA1 in breast cancer.
AU - Oeggerli, Martin
AU - Tian, Yuemin
AU - Ruiz, Christian
AU - Wijker, Barbara
AU - Sauter, Guido
AU - Obermann, Ellen
AU - Güth, Uwe
AU - Zlobec, Inti
AU - Sausbier, Matthias
AU - Kunzelmann, Karl
AU - Bubendorf, Lukas
PY - 2012
Y1 - 2012
N2 - KCNMA1 encodes the ?-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.
AB - KCNMA1 encodes the ?-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.
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Aged, 80 and over
KW - Cell Line, Tumor
KW - Gene Expression Regulation, Neoplastic
KW - Cell Proliferation
KW - Gene Amplification
KW - In Situ Hybridization, Fluorescence
KW - RNA Interference
KW - Breast Neoplasms/genetics/metabolism/pathology
KW - Estrogen Receptor alpha/genetics/metabolism
KW - Receptors, Progesterone/genetics/metabolism
KW - Ki-67 Antigen/genetics/metabolism
KW - Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/genetics/metabolism
KW - MCF-7 Cells
KW - Prostatic Neoplasms/genetics/metabolism
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Aged, 80 and over
KW - Cell Line, Tumor
KW - Gene Expression Regulation, Neoplastic
KW - Cell Proliferation
KW - Gene Amplification
KW - In Situ Hybridization, Fluorescence
KW - RNA Interference
KW - Breast Neoplasms/genetics/metabolism/pathology
KW - Estrogen Receptor alpha/genetics/metabolism
KW - Receptors, Progesterone/genetics/metabolism
KW - Ki-67 Antigen/genetics/metabolism
KW - Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/genetics/metabolism
KW - MCF-7 Cells
KW - Prostatic Neoplasms/genetics/metabolism
U2 - 10.1371/journal.pone.0041664
DO - 10.1371/journal.pone.0041664
M3 - SCORING: Journal article
VL - 7
SP - 41664
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 8
M1 - 8
ER -