Overexpression of SHP2 tyrosine phosphatase promotes the tumorigenesis of breast carcinoma.

Expression of Src homology phosphotyrosine phosphatase 2 (SHP2) has been observed in human breast cancer. SHP2 is known to promote cell migration and invasiveness. However, the pathophysiologic role of SHP2 and its relevance to tumorigenesis are still largely unknown. In the present study, we aimed to evaluate the effect of SHP2 on the malignant phenotype of human breast cancer. An SHP2-overexpressing human breast cancer cell line was established by stable transfection of the SHP2 vector. The expression of SHP2 protein was detected using western blotting. The effects of SHP2 overexpression on cell proliferation were examined by an MTS assay. Invasion and migration abilities of the SHP2-overexpressing cells were determined using a Matrigel-based Boyden chamber invasion assay and a monolayer wound-healing assay. Increased SHP2 expression was detected following SHP2-vector transfection in the MDA-MB-231 cells. Overexpression of SHP2 was associated with increased cell proliferation and clone formation, and decreased chemotherapeutic sensitivity. Furthermore, transfection of SHP2 into breast cancer cells significantly promoted tumor growth in a mouse xenograft model. The mechanism of the promotion of tumorigenesis by SHP2 appears to involve its ability to increase the activity of ERK/AKT-mediated signaling pathways. In conclusion, our data suggest an important role of SHP2 in the molecular etiology of tumor growth, and implicate the potential application of SHP2 in cancer therapy.