Wilms' Tumor 1 (WT1) as Novel Molecular Target in Breast Cancer
Abstract
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 demonstrated that WT1 protein is vital to the proliferation of breast cancer cells since downregulation of WT1 protein expression led to breast cancer growth inhibition. We also demonstrated that the WT1 protein expression is increased by 17-estradiol, but inhibited by tamoxifen or all-trans retinoic acid. We have expanded our studies and found that two other poor prognostic indicators of breast cancer patients: HER2/neu and Insulin-like Growth Factor-I use the Akt pathway to increase WT1 expression. WT1 has been shown to undergo two splicing events, which result in four different isoforms. We have preliminary data indicating that the two isoforms "A" and "D" are stimulate the proliferation of MCF-7 breast cancer cells. However, the WT1 isoforms do not appear to modulate the sensitivities of MCF-7 cells to doxorubicin and taxol. We plan to determine the mechanisms and the isoforms by which WT1 deregulates breast cancer cell proliferation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA425800
Entities
People
- Ana M. Tari
Organizations
- The University of Texas MD Anderson Cancer Center