Targeting ATM-SMC1 Pathway to Sensitize Breast Cancer Cells to Therapeutic Interventions
Abstract
Previously we have shown that ATM phosphorylates SMCl to regulate radiosensitivity. This project is to investigate whether interfering the ATM-SMCl DNA damage signaling will increase the sensitivity of breast tumor cells to radiotherapy and chemotherapy. To achieve this goal, we have synthesized two small peptides containing the original amino acid sequence of SMC 1 around Ser957. We have found that the peptide that has the Wild-type SMCl sequence possess the inhibitory ability on ATM kinase activity in vitro. We have also designed TAT-fusion peptides that can deliver the SMCl peptide into cells. We have shown that the TAT-fusion peptides: 1) can an be internalized into cells in a time-and dose-dependent manner; 2) c an a abrogate radiation- induced S-phase checkpoint; and 3) have minimal cytotoxicity to breast cancer cells in the absence of DNA damage. These insights are providing a basis for developing strategies for increasing selective tumor cell cytotoxicity after chemotherapy and radiotherapy. Future experiments will be focusing on testing the radio- and chemo-sensitization effect of the fusion peptides.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2004
- Accession Number
- ADA430434
Entities
People
- Bo Xu
Organizations
- LSU Health Sciences Center New Orleans