Wang Haifeng, Chen Tiantian, Wang Yueyue, Li Yu, Zhang Lingyu, Ding Yongxing, Chen Sulian, Wang Wenrui, Yang Qingling, Chen Changjie
Clinical Testing and Diagnosis Center, Bengbu Medical College, Bengbu 233000, China.
Department of Surgical Oncology, Bengbu Third People's Hospital, Bengbu 233000, China.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2017 Jul 25;46(4):357-363. doi: 10.3785/j.issn.1008-9292.2017.08.03.
To investigate the effect of CXC chemokine receptor 4 (CXCR4) on cell cycle of breast cancer and its molecular mechanisms.
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.
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 G/G 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.
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.
探讨CXC趋化因子受体4（CXCR4）对乳腺癌细胞周期的影响及其分子机制。
采用实时荧光定量PCR（fqRT-PCR）和蛋白质免疫印迹法检测乳腺癌细胞中CXCR4和S期激酶相关蛋白2（Skp2）的表达。采用蛋白质免疫印迹法检测信号蛋白及Skp2下游基因的表达。采用碘化丙啶染色法检测CXCR4、PI3K/Akt通路抑制剂LY294002和ERK通路抑制剂U0126对乳腺癌细胞周期的影响。
CXCR4表达下调的细胞中Skp2明显下调，CXCR4表达上调的细胞中Skp2上调。CXCR4还通过信号蛋白调节Skp2及其他下游基因的表达。CXCR4表达下调的细胞中G/G期细胞比例增加，S期细胞比例下降，联合使用LY294002或U0126时效果更明显。
CXCR4可通过PI3K/Akt和ERK信号通路调节Skp2基因表达，从而影响细胞周期并抑制乳腺癌细胞增殖。
