Targeting ATM-SMC-1 Pathway to Sensitize Breast Cancer Cells to Therapeutic Interventions
Abstract
Previously we have shown that ATM phosphorylates SMC1 to regulate radiosensitivity. This project is to investigate whether interfering the ATM-SMC1 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 SMC1 around Ser957. We have found that the peptide that has the wild-type SMC1 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 be internalized into cells in a time- and dose-dependent manner; 2) can abrogate radiation-induced S-phase checkpoint; 3) have minimal cytotoxicity to breast cancer cells in the absence of DNA damage, and more importantly 4) can significantly enhance radiation and chemotherapeutic effect. These insights have provided a basis for developing strategies for increasing selective tumor cell cytotoxicity after chemotherapy and radiotherapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2005
- Accession Number
- ADA447646
Entities
People
- Bo Xu
Organizations
- Louisiana State University