CDK2-AP1 inhibits growth of breast cancer cells by regulating cell cycle and increasing docetaxel sensitivity in vivo and in vitro.

Autor: He X; Department of Breast Surgery, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022 China., Xiang H; Department of Pathology, First Affiliated Hospital of College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003 China., Zong X; 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., Yan X; Department of Breast Surgery, Shanghai Jiao Tong University affiliated Shanghai sixth Hospital, 600 Yishan Road, Shanghai, 200233 China., Yu Y; Department of Breast Surgery, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022 China., Liu G; Department of Radiotherapy, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022 China., Zou D; Department of Breast Surgery, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022 China., Yang H; Department of Breast Surgery, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022 China.
Jazyk: angličtina
Zdroj: Cancer cell international [Cancer Cell Int] 2014 Nov 30; Vol. 14 (1), pp. 130. Date of Electronic Publication: 2014 Nov 30 (Print Publication: 2014).
DOI: 10.1186/s12935-014-0130-8
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz: