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Journal of ZheJiang University(Medical Science)  2017, Vol. 46 Issue (4): 357-363    DOI: 10.3785/j.issn.1008-9292.2017.08.03
CXC chemokine receptor 4 regulates breast cancer cell cycle through S phase kinase associated protein 2
WANG Haifeng1, CHEN Tiantian1, WANG Yueyue1, LI Yu1, ZHANG Lingyu1, DING Yongxing2, CHEN Sulian3, WANG Wenrui4, YANG Qingling3, CHEN Changjie3
1. Clinical Testing and Diagnosis Center, Bengbu Medical College, Bengbu 233000, China;
2. Department of Surgical Oncology, Bengbu Third People's Hospital, Bengbu 233000, China;
3. Department of Biochemistry & Molecular Biology, Bengbu Medical College, Bengbu 233000, China;
4. Department of Biotechnology, Bengbu Medical College, Bengbu 233000, China
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Objective:To investigate the effect of CXC chemokine receptor 4 (CXCR4) on cell cycle of breast cancer and its molecular mechanisms. Methods:The expression of CXCR4 and S phase kinase associated protein 2 (Skp2) was detected by real-time fluorescence quantitative PCR (fqRT-PCR) and Western blot in breast cancer cells. The expression of signal proteins and the downstream genes of Skp2 was detected by Western blot. The effect of CXCR4, PI3K/Akt pathway inhibitor LY294002 and ERK pathway inhibitor U0126 on cell cycle of breast cancer was detected by propidium iodide staining. Results:Skp2 was significantly down-regulated in CXCR4-downregulated cells and up-regulated in CXCR4-upregulated cells. CXCR4 also regulated the expression of Skp2 and other downstream genes by signaling protein. The proportion of cells in G0/G1 phase increased and that in S phase declined in CXCR4-downregulated cell, and the effect was more significant when combined with the use of LY294002 or U0126. Conclusion:CXCR4 can affect cell cycle and inhibit the proliferation of breast cancer cells by regulating Skp2 gene expression through PI3K/Akt and ERK signaling pathway.

Key wordsBreast neoplasms/physiopathology      Receptors, CXCR4/biosynthesis      Receptors, CXCR4/genetics      S-phase kinase-associated proteins/metabolism      Cell line, tumor/metabolism      Cell proliferation      Cell cycle     
Received: 16 February 2017      Published: 25 August 2017
CLC:  R737.9  
Cite this article:

WANG Haifeng, CHEN Tiantian, WANG Yueyue, LI Yu, ZHANG Lingyu, DING Yongxing, CHEN Sulian, WANG Wenrui, YANG Qingling, CHEN Changjie. CXC chemokine receptor 4 regulates breast cancer cell cycle through S phase kinase associated protein 2. Journal of ZheJiang University(Medical Science), 2017, 46(4): 357-363.

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关键词: 乳腺肿瘤/病理生理学,  受体,  CXCR4/生物合成,  受体,  CXCR4/遗传学,  S期激酶相关蛋白质类/代谢,  细胞系,  肿瘤/代谢,  细胞增殖,  细胞周期 

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