title: CDK2-AP1 inhibits growth of breast cancer cells by regulating cell cycle and increasing docetaxel sensitivity in vivo and in vitro.
abstract: BACKGROUND
  Cell cycle regulatory pathway is a well-established pathway mainly dependent on cyclin-dependent kinases (CDKs), which are regulated positively by cyclins and negatively by cyclin-dependent kinase inhibitors(CKIs). Cyclin-dependent kinase 2 associate protein 1(CDK2-AP1) is a specific negative regulatory protein for CDK2, is important in the cancer cell cycle. However, the function of CDK2-AP1 in breast cancer remains unclear. We designed therefore explored the effects of CDK2-AP1 on breast cancer growth and its chemo-sensitivity.
  
  
  METHODS
  Expression of CDK2-AP1, CDK2 and CyclinD1 in 209 cases of pathological specimens using IHC staining was measured. Lost-of-function and Gain-of-function assays were used in vivo and in vitro relating to the specific role of CDK2-AP1 in breast cancer. We analyzed in vivo and in vitro the impact of CDK2-AP1 on chemotherapy sensitivity in breast cancer.
  
  
  RESULTS
  The positive ratio of CDK2-AP1 expression was reduced successively in normal breast tissue, DCIS, invasive breast cancer and relapsed breast cancer, however, with CDK2 and CyclinD1 it was suggested that CDK2-AP1 was correlated closely with the tumorigenesis and progress, and might work as a tumor suppressor. After down-regulating CDK2-AP1 in breast cancer cells, the cell cycle was accelerated and cell proliferation enhanced. The cell cycle was arrested in G0/G1 phase and G2/M phase after up-regulating CDK2-AP1 in breast cancer cells, inhibiting cell proliferation. The expression of CDK2 and CyclinD1 changed accordingly after downregulation or upregulation of CDK2-AP1 by western blot, suggesting a role of the CDK2-AP1/CDK2/CyclinD1 cell cycle pathway in the initiation and progression of breast cancer. Similar results were obtained in animal assays. The data indicates that CDK2-AP1 can induce sensitivity to docetaxel treatment in breast cancer cells.
  
  
  CONCLUSIONS
  CDK2-AP1 affects tumorigenesis, tumor growth and chemo-sensitivity by cell cycle regulation, which can potentially to be a therapeutical agent in breast cancer.
authors.affiliation: Department of Breast Surgery, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022 China.
authors.forename: Xiangming
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Pathology, First Affiliated Hospital of College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003 China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xiang
authors.affiliation: Department of Breast Surgery, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022 China ; Department of Breast Surgery, Shanghai Jiao Tong University affiliated Shanghai sixth Hospital, 600 Yishan Road, Shanghai, 200233 China.
authors.forename: Xiangyun
authors.initials: X
authors.lastname: Zong
authors.affiliation: Department of Breast Surgery, Shanghai Jiao Tong University affiliated Shanghai sixth Hospital, 600 Yishan Road, Shanghai, 200233 China.
authors.forename: Xuebing
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Breast Surgery, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022 China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Radiotherapy, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022 China.
authors.forename: Guan
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Breast Surgery, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022 China.
authors.forename: Dehong
authors.initials: D
authors.lastname: Zou
authors.affiliation: Department of Breast Surgery, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022 China.
authors.forename: Hongjian
authors.initials: H
authors.lastname: Yang
keywords: Breast cancer; CDK2-AP1; Cell cycle; Chemotherapy sensitivity