Characterizing and Targeting Replication Stress Response Defects in Breast Cancer
Abstract
During the second year of this project, we have made significant progress in several of our proposed tasks. We found that both TUSC4 and PRMT5 may function as RSR genes through their activities in facilitating HR DNA repair. Both TUSC4 and PRMT5 inhibit cell proliferation and cellular transformation, and may function as potential tumor suppressor genes in breast cancer. DNA2 is also involved in HR repair in response to RSR. However, unlike TUSC4 or PRMT5, DNA2 may exert an oncogenic function in cancer cells. In addition, we identified and validated APP as an RSR-defect-specific membrane protein and have successfully conjugated APP antibody to hollow gold nanoparticles, an important step for developing nano-imaging and nano-targeting in the future. We also identified additional RSR-defect-specific membrane molecules by SILAC. We will seek to determine if any of these molecules may serve as a better marker than APP for detecting and targeting RSR-defect cells. Finally, using Prestwick chemical library, we have successfully completed our screen for drugs that may specifically target on RSR-defect cells. We will evaluate the sensitivity and specificity of these drugs on killing the RSR-defect cells soon.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2012
- Accession Number
- ADA567575
Entities
People
- Chun Li
- Chun-jen Lin
- Edward Wang
- Hui Dai
- Ju-Seog Lee
- Shiaw-Yih Lin
Organizations
- The University of Texas MD Anderson Cancer Center