Abstract:

Objective To investigate the relationship between RSK4 expression and Ki-67，cyclin D1，CXCR4 and E-cadherin levels in an in vivo tumor model of breast cancer in order to explore the mechanism of breast cancer development. Methods The experimental group of nude mice was subcutaneously injected with MCF-7 cells transfected with siRNA （RSK4-RNAi-LV），while the negative control group was subcutaneously injected with MCF-7 cells transfected with siRNA （NC-GFP-LV），and a blank control group was subcutaneously injected with MCF-7 cells alone. Expression of RSK4，Ki-67，cyclin D1，CXCR4 and E-cadherin in samples of transplanted tumors was observed by immunohistochemistry. Results Levels of RSK4 and E-cadherin protein were 3.2±0.5% and 28.2±0.7% in the experimental group，which was significantly lower than in the blank control group （36.7±3.4%，51.7±4.2%） and negative control group（61.1±5.1%，49.2±3.8%） （F=56.79 and 61.89，P<0.05）. Similar，expression levels of Ki-67，cyclin D1，and CXCR4 in the experimental group were，respectively，67.8±5.8%，61.7±4.6%，and 56.3±3.9%，which were significantly higher than in the blank control group（34.5±1.4%，29.7±2.5%，30.7±3.1%） and the negative control group （29.8±1.9%，35.7±4.6%，28.5±3.7%） （F=45.24，52.16，and 61.24，P<0.05）. RSK4 protein expression showed a significant negative correlation with Ki-67（r=-0.857，P<0.001），cyclin D1（r=-0.826，P<0.001） and CXCR4 （r=-0.867，P<0.001）. RSK4 protein expression showed a significant positive correlation with E-cadherin（r=0.879，P<0.001）. Conclusions RSK4 knockdown may affect the expression of tumor proliferation factor and invasion factor，promoting the proliferation and metastasis of breast cancer cells. RSK4 may regulate genes in a way that promotes breast cancer cell proliferation and invasion，including up-regu-lation of CXCR4，Ki-67，and CyclinD1，as well as down-regulation of E-cadherin.

Key words: Breast neoplasms, RSK4, Ki-67, cyclin D1, CXCR4, E-cadherin, MCF-7 cell line, Transplantation tumor