Abstract
BackgroundA capillary network is needed in cancer growth and metastasis. Induction of angiogenesis represents one of the major hallmarks of cancer. CDK11p58, a Ser/Thr kinase that belongs to the Cell Division Cycle 2-like 1 (CDC2L1) subfamily is associated with cell cycle progression, tumorigenesis, sister chromatid cohesion and apoptotic signaling. However, its role in breast cancer proliferation and angiogenesis remains unclear.MethodsTumorigenicity assays and blood vessel assessment in athymic mice were used to assess the function of CDK11p58 in tumor proliferation and angiogenesis. CCK-8 assay was used to detect breast cancer cell growth. Immunohistochemistry was used to detect the expression of vascular endothelial growth factor (VEGF), CD31 and CD34 in CDK11 positive patient breast cancer tissues. Dual-Luciferase array was used to analyze the function of CDK11p58 in the regulation of VEGF promoter activity. Western blot was used to detect related protein expression levels.ResultsCDK11p58 inhibited breast cancer growth and angiogenesis in breast cancer cells and in nude mice transplanted with tumors. Immunohistochemistry confirmed that CDK11p58 was negatively associated with angiogenesis-related proteins such as VEGF, CD31 and CD34 in breast cancer patients. Real-time PCR and dual-luciferase assay showed CDK11p58 inhibited the mRNA levels of VEGF and the promoter activity of VEGF. As CDK11p58 is a Ser/Thr kinase, the kinase-dead mutant failed to inhibit VEGF mRNA and promoter activity. Western blot analysis showed the same pattern of related protein expression. The data suggested angiogenesis inhibition was dependent on CDK11p58 kinase activity.ConclusionThis study indicates that CDK11p58 inhibits the growth and angiogenesis of breast cancer dependent on its kinase activity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1698-7) contains supplementary material, which is available to authorized users.
Highlights
A capillary network is needed in cancer growth and metastasis
By Cell Counting Kit-8 assay, we found that CDK11p58 inhibited breast cancer cell gowth compared with the pBABE control both in MDA-MB231 and T47D cells (Fig. 1b)
In this study, we focused on the critical role of CDK11p58 in breast cancer growth and angiogenesis, especially the regulation of vascular endothelial growth factor (VEGF) by CDK11p58 and the dependence on its kinase activity
Summary
A capillary network is needed in cancer growth and metastasis. Induction of angiogenesis represents one of the major hallmarks of cancer. Its role in breast cancer proliferation and angiogenesis remains unclear. A capillary network from the surrounding host tissue is needed both in cancer proliferation and in cancer metastasis [2]. Induction of angiogenesis represents one of the major hallmarks of cancer [4], and plays important roles in wound healing, endothelial cell-mediated degradation of the extracellular matrix, and the transition of benign tissues into solid tumors [5]. We found that CDK11p58 inhibited the proliferation of prostate cancer and was involved in regulation of androgen and estrogen signaling [12,13,14]. Our previous study demonstrated that CDK11p58 inhibited ERα-positive breast cancer invasion by targeting integrin β3 via the repression of ERα signaling [15] and we found breast cancers transfected with CDK11p58 grew slowly compared with the control cell lines, so we speculated that CDK11p58 might inhibit the growth of breast cancer
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