Abstract
Purpose: Tientsin Albino 2 (TA2) mice have a high incidence of spontaneous breast cancer. Tumor initiation is related to mouse mammary tumor virus (MMTV) infection. MMTV is hormonally regulated and may promote tumor formation via Wnt/β-catenin signaling pathway. This study attempts to clarify the relationship between β-catenin expression and the initiation and metastasis of spontaneous breast cancer in TA2 mice. Materials and Methods: Pathological samples illustrating the development of spontaneous breast cancer in TA2 mice were collected and the presence of virus particles was verified in the cancer tissue by electron microscope. Expression of Wnt/β-catenin signaling-pathway-related proteins including β-catenin, Wnt 5a, GSK-3β, and cyclin D1 were detected. MA-891 cell line derived from TA2 spontaneous breast cancer was cultured and siRNA was used to inhibit the expression of β-catenin in the primary culture cell line. Cell cycle analyses and comparisons of the invasiveness and migration capability of tumor cells were performed before and after β-catenin inhibition. Downstream protein expression of β-catenin was studied by western blot, co-immunoprecipitation assay. Tumorigenesis and metastasis were compared with that of negative control, siRNA control, and siRNA β-catenin-1512. Furthermore, proteins related to the proliferation and invasion of tumor were detected by western blot. Results: β-catenin expression was found to be located in the membrane and cytoplasm in normal mammary tissue and precancerous lesions, respectively. However, in the breast cancer tissue, β-catenin expression was located in the nuclei. After transfection with siRNA-1512, the cells showed decreased proliferation, invasiveness and migration capability, tumorigenicity, and metastasis, and the expression of the proteins related to tumor proliferation and metastasis such as c-myc, Cyclin D1, MMP-9, and VEGF were down-regulated. Conclusion: These results confirmed that the expression and location of β-catenin were associated with the initiation and metastasis of spontaneous breast cancer in TA2 mice.