CXC chemokine receptor 4 regulates breast cancer cell cycle through S phase kinase associated protein 2.
- Author:
Haifeng WANG
1
;
Tiantian CHEN
1
;
Yueyue WANG
1
;
Yu LI
1
;
Lingyu ZHANG
1
;
Yongxing DING
2
;
Sulian CHEN
3
;
Wenrui WANG
4
;
Qingling YANG
3
;
Changjie CHEN
5
Author Information
- Publication Type:Journal Article
- From: Journal of Zhejiang University. Medical sciences 2017;46(4):357-363
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of CXC chemokine receptor 4 (CXCR4) on cell cycle of breast cancer and its molecular mechanisms.
METHODSThe 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.
RESULTSSkp2 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/Gphase 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.
CONCLUSIONSCXCR4 can affect cell cycle and inhibit the proliferation of breast cancer cells by regulating Skp2 gene expression through PI3K/Akt and ERK signaling pathway.
