Role of KCNMA1 in breast cancer.
Role of KCNMA1 in breast cancer.
复制标题
DOI：
10.1371/journal.pone.0041664
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Bubendorf L
中科院分区：
文献类型：
--
作者：
Oeggerli M;Tian Y;Ruiz C;Wijker B;Sauter G;Obermann E;Güth U;Zlobec I;Sausbier M;Kunzelmann K;Bubendorf L
KCNMA1编码大电导、电压和钙激活(BK)钾通道的α亚基，已被报道为前列腺癌10q22处基因组扩增的靶基因。为了研究KCNMA1基因扩增在人类其他肿瘤中的发生率，采用荧光原位杂交(FISH)技术对118种不同肿瘤类型的2445例肿瘤组织中KCNMA1基因的拷贝数进行了分析。KCNMA1扩增仅限于一小部分乳腺癌、卵巢癌和子宫内膜癌，浸润性导管癌和卵巢浆液性癌和子宫内膜癌的发生率最高(3-7%)。我们对1200个与预后有关的肿瘤的乳腺癌组织微阵列(TMA)进行了广泛的分析。KCNMA1基因扩增与高肿瘤分期、高分级、高肿瘤细胞增殖和预后不良显著相关。免疫荧光显示KCNMA1蛋白在9例乳腺癌中的8例和乳腺癌细胞系MFM223中有中等或强表达。通过全细胞膜片钳记录和增殖分析，使用siRNA敲除、BK通道激活剂17？雌二醇和BK通道阻断剂paxilline，证实KCNMA1在乳腺癌细胞系中的功能。我们的研究结果表明，KCNMA1的表达增强与乳腺癌的高增殖率和恶性程度有关，并参与了乳腺癌的高增殖率和恶性程度。
KCNMA1 encodes the α-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 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.
登录
查看更多内容
影响因子：
3.8
作者：
Khaitan D;Sankpal UT;Weksler B;Meister EA;Romero IA;Couraud PO;Ningaraj NS
通讯作者：
Ningaraj NS
绝经后妇女的雄激素受体表达和乳腺癌存活。
DOI：
10.1158/1078-0432.ccr-10-2021
发表时间：
2011-04-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Hu R;Dawood S;Holmes MD;Collins LC;Schnitt SJ;Cole K;Marotti JD;Hankinson SE;Colditz GA;Tamimi RM
通讯作者：
Tamimi RM
影响因子：
6.4
作者：
Magklara, A;Brown, TJ;Diamandis, EP
通讯作者：
Diamandis, EP
影响因子：
1.7
作者：
Basrai, D;Kraft, R;Patt, S
通讯作者：
Patt, S
影响因子：
8
作者：
Bloch, M.;Ousingsawat, J.;Bubendorf, L.
通讯作者：
Bubendorf, L.