Effects of breast cancer cells stably overexpressing RSK4 on growth of transplanted human breast cancer in severe combined immunodeficiency mice

Abstract

To construct a breast cancer cell line MD-MB-231 stably overexpressing RSK4 gene and study its in vivo effects on tumor tumorigenesis. The MD-MB-231 cells were transfected with pcDNA3.1/Neo and pcDNA3.1/Neo-RSK4 by lipofectamin transfection respectively. The stable expression of RSK4 (MR11 and MR12) and control vector (MN10 and MN11) were inoculated into severe combined immunodeficiency (SCID) mice subcutis to establish a model of human breast cancer in SCID mice. The xenograft tumor growth, invasion and metastasis were observed after 6 - 10 weeks. The stable cell lines MR11, MR12 and MN10, MN11 were screened successfully. We constructed the human breast cancer transplanted model and dissected SCID mice. After 6 weeks, SCID mice subcutis of the MN10/MN11 group yielded 10/10 metastatic tumors versus 6/10 and 7/10 in the MR11/MR12 group respectively. MR11 and MR12 showed much smaller tumor sizes and significantly reduced tumor volume and weight versus MN10 and MN11 (P < 0.001). In the control group, visceral metastasis developed in 80% (8/10) of mice while in metastasis developed in 40% (4/10) of mice injected with RSK4-overexpressing MDA-MB-231 cells. Histological examination of hematoxylin and eosin-stained paraffin sections of lungs revealed numerous metastases in mice injected with vector control cells whereas RSK4-overexpressing cells showed markedly decreased metastatic lesions. Transplanted human breast cancer in SCID mice closely correlates with the disease course of clinical tumor patients. Overexpression of RSK4 can inhibit tumor growth of transplanted human breast cancer in SCID mice.