title: Critical role of CDK11(p58) in human breast cancer growth and angiogenesis.
abstract: BACKGROUND
  A capillary network is needed in cancer growth and metastasis. Induction of angiogenesis represents one of the major hallmarks of cancer. CDK11(p58), 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.
  
  
  METHODS
  Tumorigenicity assays and blood vessel assessment in athymic mice were used to assess the function of CDK11(p58) 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 CDK11(p58) in the regulation of VEGF promoter activity. Western blot was used to detect related protein expression levels.
  
  
  RESULTS
  CDK11(p58) inhibited breast cancer growth and angiogenesis in breast cancer cells and in nude mice transplanted with tumors. Immunohistochemistry confirmed that CDK11(p58) 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 CDK11(p58) inhibited the mRNA levels of VEGF and the promoter activity of VEGF. As CDK11(p58) 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 CDK11(p58) kinase activity.
  
  
  CONCLUSIONS
  This study indicates that CDK11(p58) inhibits the growth and angiogenesis of breast cancer dependent on its kinase activity.
authors.affiliation: Department of Breast Surgery, Breast Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. yychi@126.com.
authors.forename: Yayun
authors.initials: Y
authors.lastname: Chi
authors.affiliation: Department of Breast Surgery, Breast Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. sammer312@126.com.
authors.forename: Sheng
authors.initials: S
authors.lastname: Huang
authors.affiliation: School of Biomedical Engineering, hanghai Jiao Tong University, Shanghai, 200240, China. vjackpeng@sjtu.edu.cn.
authors.forename: Haojie
authors.initials: H
authors.lastname: Peng
authors.affiliation: Department of Breast Surgery, Breast Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. purpurmy@gmail.com.
authors.forename: Mengying
authors.initials: M
authors.lastname: Liu
authors.affiliation: School of Biomedical Engineering, hanghai Jiao Tong University, Shanghai, 200240, China. junzhao@sjtu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Breast Surgery, Breast Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. zhimingshao@yahoo.com.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Shao
authors.affiliation: Department of Breast Surgery, Breast Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. wujiong1122@vip.sina.com.
authors.forename: Jiong
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D056743:Cyclin D3 / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D056743:Cyclin D3; D042461:Vascular Endothelial Growth Factor A; C584437:CDK19 protein, human; D018844:Cyclin-Dependent Kinases