Wilms Tumor 1 (WT1) as Novel Molecular Target in Breast Cancer

摘要

High levels of Wilms' Tumor 1 (WT1) mRNA in breast tumors have been linked with poor prognosis for breast cancer patients. However, the function of WT1 protein in breast cancer was not known. We reported the expression of WT1 protein in 9 out of 10 human breast cancer cell lines. The levels of WT1 protein were increased by the HER2/neu oncogene and 17 -estradiol. We demonstrated that WT1 protein is vital to the proliferation of breast cancer cells since down regulation of WT1 protein expression led to breast cancer growth inhibition and apoptosis, which was correlated with decreased cyclin D1 and Bcl-2 levels. WT1 has been shown to undergo two splicing events, which result in four different isoforms. Stable transfection of the different WT1 isoforms was performed in MCF-7 cells. Our data indicate that the WT1 isoforms enhance the in vitro proliferation of MCF-7 breast cancer cells, but do not modulate the sensitivities of MCF-7 cells to doxorubicin, taxol, or tamoxifen. WT1 protein enhances breast tumorigenesis induced by other oncogenes or growth factors, such as HER2/neu and estradiol, but its over expression alone is not sufficient to induce breast tumorigenesis.