Role of DNA-Dependent Protein Kinase in Breast Cancer Development/Progression
Abstract
DNA-dependent protein kinase (DNA-PK) is a nuclear serine/threonine protein kinase involved in various DNA metabolism and damage signaling pathways. DNA damage activates DNA-PK, which in turn phosphorylates a number of key proteins involved in replication, repair, and transcription. Accordingly, DNA-PK has long been suspected as a factor involved in sensing and transmitting DNA damage signals to the downstream target, which eventually contributes to the genomic stability and prevention of cancer. The overall goal of this proposal is to explore the role of DNA-PK in the development and progression of breast cancer. Since DNA-PK is a DNA repair factor as well as involved in damage signaling pathway, levels of DNA-PK activity among breast cancer would contribute to their drug resistance and also provide the basis for selection of patients for treatment with chemotherapy drugs. From the first two years of our study, we concluded that a peptide-based inhibitor preventing DNA-PKcs from forming a complex with Ku70/Ku80 significantly lowered DNA-PK activity. Furthermore, treatment of these breast cancer cells with target peptide significantly lowered the cell growth only in the presence of ionizing radiation, indicating that the peptide-based inhibitor exhibited a positive effect of on lowering drug resistance by specifically targeting DNA-PK in vivo. This result also validates a physiologic role for DNA-PK in chemotherapy drug resistance of breast cancers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA408211
Entities
People
- Suk-hee Lee
Organizations
- Indiana University