CDK11p58 inhibits ERα-positive breast cancer invasion by targeting integrin β3 via the repression of ERα signaling.
CDK11p58 inhibits ERα-positive breast cancer invasion by targeting integrin β3 via the repression of ERα signaling.
复制标题
DOI：
10.1186/1471-2407-14-577
复制
发表时间：
2014-08-08
期刊：
影响因子：
3.8
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Chi Y;Huang S;Wang L;Zhou R;Wang L;Xiao X;Li D;Cai Y;Zhou X;Wu J
CDK 11 p58是一种丝氨酸/苏氨酸激酶，属于细胞分裂周期2样蛋白1（CDC 2L 1）亚家族，与细胞周期进程、肿瘤发生和凋亡信号相关。CDK 11 p58还参与类固醇受体的调节，例如雄激素和雌激素受体。我们以前发现CDK 11 p58在前列腺癌中异常表达。然而，它在乳腺癌中的作用仍不清楚。CDK 11 p58表达通过组织阵列中的免疫组织化学染色来评估。用Transwell法检测乳腺癌细胞的侵袭和转移。使用TaqMan®转移基因表达测定来搜索CDK 11 p58信号传导途径中的潜在下游因子。使用qRT-PCR评估mRNA水平，并使用双荧光素酶阵列分析启动子活性。Western blotting检测蛋白水平。CDK 11 p58的表达与淋巴结状态（P = 0.012）、复发状态（P = 0.002）和转移状态（P = 0.023）呈负相关。Kaplan-Meier生存曲线显示，CDK 11低表达的乳腺癌患者无病生存期（DFS）明显较差。有趣的是，使用乳腺癌细胞系ZR-75-30和MDA-MB-231，我们发现CDK 11 p58能够以激酶依赖的方式抑制ERα阳性乳腺癌细胞的迁移和侵袭，而不是ERα阴性乳腺癌细胞。基因表达分析表明CDK 11 p58显著抑制整合素β3 mRNA的表达，荧光素酶结果证实CDK 11 p58通过ERα抑制整合素β3启动子。整合素β3的表达与ERα信号高度相关; ERα过表达刺激整合素β3的表达，而siRNA介导的ERα敲低减弱整合素β3的表达。这些数据表明，CDK 11 p58是ERα阳性乳腺癌中的抗转移基因，并且CDK 11 p58通过抑制ERα信号传导来调节整合素β3可能构成乳腺癌侵袭的信号传导途径的一部分。
CDK11p58, a Ser/Thr kinase that belongs to the cell division cycle 2-like 1 (CDC2L1) subfamily, is associated with cell cycle progression, tumorigenesis and apoptotic signaling. CDK11p58 is also involved in the regulation of steroid receptors, such as androgen and estrogen receptors. We previously found that CDK11p58 was abnormally expressed in prostate cancer. However, its role in breast cancer remains unclear. CDK11p58 expression was evaluated by immunohistochemical staining in a tissue array. A Transwell assay was used to detect invasion and metastasis in breast cancer cells. The TaqMan® Metastasis Gene Expression Assay was used to search for potential downstream factors in the CDK11p58 signaling pathway. qRT-PCR was used to evaluate mRNA levels, and the dual luciferase array was used to analyze promoter activity. Western blotting was used to detect the protein level. CDK11p58 expression was negatively correlated with node status (P = 0.012), relapse status (P = 0.002) and metastasis status (P = 0.023). Kaplan-Meier survival curves indicated that the disease-free survival (DFS) was significantly poor in breast cancer patients with low CDK11 expression. Interestingly, using the breast cancer cell lines ZR-75-30 and MDA-MB-231, we found that CDK11p58 was capable of repressing the migration and invasion of ERα-positive breast cancer cells, but not ERα-negative breast cancer cells, in a kinase-dependent manner. Gene expression assays demonstrated that integrin β3 mRNA was dramatically repressed by CDK11p58, and luciferase results confirmed that the integrin β3 promoter was inhibited by CDK11p58 through ERα repression. The expression of integrin β3 was highly related to ERα signaling; ERα overexpression stimulated integrin β3 expression, whereas siRNA-mediated knockdown of ERα attenuated integrin β3 expression. These data indicate that CDK11p58 is an anti-metastatic gene in ERα-positive breast cancer and that the regulation of integrin β3 by CDK11p58 via the repression of ERα signaling may constitute part of a signaling pathway underlying breast cancer invasion.
登录
查看更多内容
DOI：
10.1186/bcr1752
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Guo HQ;Gao M;Ma J;Xiao T;Zhao LL;Gao Y;Pan QJ
通讯作者：
Pan QJ
影响因子：
3.8
作者：
Han W;Han MR;Kang JJ;Bae JY;Lee JH;Bae YJ;Lee JE;Shin HJ;Hwang KT;Hwang SE;Kim SW;Noh DY
通讯作者：
Noh DY
影响因子：
3.7
作者：
BORG, A;ZHANG, QX;WENNGREN, E
通讯作者：
WENNGREN, E
影响因子：
10.5
作者：
Schlisio, Susanne;Kenchappa, Rajappa S.;Kaelin, William G., Jr.
通讯作者：
Kaelin, William G., Jr.
影响因子：
7.7
作者：
Petretti, C;Savoian, M;Giet, R
通讯作者：
Giet, R