Effects Of Tyrosine Phosphatase Shp2 On The Regulation Of Estrogen Signaling Pathway In Breast Cancer

Shp2(The Src homology phosphotyrosylphosphatase 2) is over-expressed in most of cases of breast cancer and play an important role in breast tumorigeneisis. However,the detail of shp2 actions is poorly understood.In the current studies,we investigated effects of Shp2 on basic or estrogen-mediated cell growth in breast cancer cell lines.The results showed that:(1) cell growth was inhibited when protein level of Shp2 was decreased by interference small RNAs of Shp2 in breast cancer cell line MCF7 and MDA-MB-231;(2) estrogen induced the expression of Shp2 in dose dependent manner in MCF7 and Bcap-37 cells;(3) the inhibitors of Shp2 activity,pshp1 or pshp4,strongly blocked the estrogen-stimulated cell proliferation in MCF7 cells;(4) pshp1 or pshp4 suppressed the estrogen-mediated transcription of target gene TFF1.In addition,deletion of Shp2 protein also repressed the effects of estrogen on TFF1 transcription;(5) estrogen stimulated formation of a complex involing ERα,IGF-IR,Shp2 and Gab2 in a dose-dependent fasion;(6) estrogen activated IGF-IR or Akt in MCF7 cells,and inhibitors of the phosphorylation of IGF-IR or Akt decreased the mRNA level of TFF1(pS2) induced by estrogen treatment.Taken together,these results suggested that shp2 play important roles in breast tumorigenesis by the regulation on estrogen signaling pathway,and provide a novel mechanism.On the basis of these premises,we believe that more works deserved to be investigated the roles of Shp2 in estrogen signaling pathway.Shp2 may serves as a new therapeutic target against breast cancer.