The Regulation Of Shp2on The Breast Tumorigenesis In Animal Model

Breast cancer is one of the major disease threats to women’s health and life, and it hasbecome the top one in women’s malignant tumor list. Although the mechanism of breastcancer has the very deep understanding, the progress of the diagnosis and treatment of breastcancer is still not too big. Tumor is thought as the outcome of a series of cell regulationdisorders involving a variety of signal transduction, especially protein kinase signal. However,the current understanding of these signals is not sufficient. The human gene ptpn11(codedprotein tyrosine phosphatase Shp2) is easy to be mutated. Mutants of ptpn11gene areassociated with leukemia, stomach cancer, liver cancer and other tumors. So ptpn11isconsidered a proto-oncogene. In breast cancer, Shp2is over-expressed in the most of cases,and cell experiments also demonstrate that Shp2involved in the occurrence of breast tumor.But the evidences of the regulation in vivo of Shp2on breast cancer are still lacking.Disease animal model is commonly used as research tools. Here, our studies will usesome breast tumor animal models to investigate the role of Shp2in the development of breastcancer in vivo. First, DMBA induced rat breast tumor animals were treated with the activityinhibitor (Phps1) of Shp2. The incubation period of the breast tumor was lengthened, and theoccurrence of the tumor was delayed. The proportion of DMBA-induced tumor wassignificantly reduced (P <0.05). At each observation point, total number of tumors inPhps1-treated animals was less than that of the control animals. In the last time, the finalnumber of tumors in Phps1-treated animals has a reduction of7~10%. But the tumor growthwas not blocked despite the number of tumor in experimental group is less than that in thecontrol group; the tumor size has no significant difference between the two group. In DMBAinduced rat breast tumor, the expression of Shp2protein is increased. Another, thephosphorylation of Erk protein in breast tumor was decreased with Phps1treatment. Second,we also treated MMTV-Pyvt transgenic mice with the Shp2inhibitor, and found that thegrowth of breast tumor was inhibited. Tumor size in experimental mice was significantlysmaller than that in the control group.These results are preliminary evidence that shp2involved in regulating the occurrence of breast tumor in vivo.