Dynamic Wnt Gene Expression In The Oncogenesis Of Breast Cancer In TA2Mice And Experimental Therapeutic Effect Of Sunitinib On TA2Spontaneous Breast Cancer

Objective1. To collect of TA2spontaneous breast cancer in mice to observe the characteristics of their tumors.2. Dynamic expression of Wnt family members in the generation of TA2mice breast cancer were investigated in this study.3. The TA2mice spontaneous breast cancer with high metastastic potential was treated with sunitinib, then the result of the treatment was studied, inorder to find a new therapy for triple negative breast cancer.Methods1. Spontaneous breast cancers were harvested from42female TA2mice and mammary glands were collected from normal TA2mice and pregnant TA2mice.2. Gene chip result showed that differential-expressed genes between breast cancer and normal mammary gland include several Wnt gene family members, which was validated by real time PCR and finding their expression variation in the generation of TA2mouse breast cancer.3. The tissue of TA2mice spontaneous breast cancer with high metastastic potential was grinded to single cell suspension, which was injected into the abdominal subcutaneous of normal TA2to purify breast cancer cells with high metastastic potential. When tumors grew to a suitable volume, TA2mice was treated with sunitinib.Result1. Spontaneous breast cancers were harvested from42female TA2mice, which are produced female. On pathological diagnosis, TA2mice spontaneous tumors are breast cancer, estrogen receptor, progesterone receptor and human epidermal growth factor receptor2were negative. The average age of the TA2mice at carcinogenesis was336.706±85.05days, and the average frequency of delivery was3.767±1.79. those whose delivery frequency more than3times accounteds for71.42%of the total number of the42mice. The MAX of frequency of delivery was7, whose mean age at tumorigenesis was only251.5d, which far below the average.2. Contrast to normal TA2mouse mammary gland, Wnt1, Wnt5a and Wnt10b were obviously up-regulated in TA2mice breast cancer tissue, but wnt5b was expressed in the opposite direction between normal TA2mouse mammary gland and breast cancer. The relative expression level ofWntl gradually increased during pregnancy, and after childbirth was higher than normal virgin mice; Early in pregnancy WntlOb relative expression levels increased, then declined,and increased again late in pregnancy. After childbirth it has decreased a little, but still higher than normal virgin mice Wnt5a relative expression levels decreased gradually during pregnancy, after delivery below normal virgin mice. Wnt5b relative expression level increased first and then decreased during pregnancy, after delivery Wnt5b expression levels are higher than normal virgin mice.3. Treat the TA2mice spontaneous breast cancer with high metastastic potential with sunitinb. The result suggested that in the experimental group, tumor growth rate was significantly lower than the control group. In addition, in the experimental group, lung, liver, spleen, kidney and other internal organs and abdominal metastasis rate was significantly lower than the control group; necrosis in cancer tissue is larger; number of PCNA-positive cancer cells was significantly lower than the control group,and.MVD was reduced.Conclusion1. A statistical analysis of42TA2mice with spontaneous breast cancer showed that more times of delivery, the higher the incidence of breast cancer,2. the yonger the TA2mice at carcinogenesis.3. Wnt1、Wnt5a and WntlOb might promote breast cancer development, while Wnt5b play a inhibitor in TA2breast cancer development.4. The antineoplastic agents sunitinib significantly inhibited TA2spontaneous breast cancer.