Assessment of the role of translationally controlled tumor protein 1 (TPT1/TCTP) in breast cancer susceptibility and ATM signaling.

BACKGROUND AND PURPOSE

The translationally controlled tumor protein 1 (TPT1/TCTP) has been implicated in the intracellular DNA damage response. We tested the role of TPT1 in breast cancer (BC) predisposition and re-evaluated its function in Ataxia-Telangiectasia mutated (ATM)-mediated damage recognition and DNA repair.

MATERIAL AND METHODS

The coding sequence was scanned for mutations in genomic DNA from 200 breast cancer patients. was down-regulated through siRNA in breast epithelial and fibroblast cell cultures. ATM activation after irradiation (IR) was analyzed by western blotting, and γH2A.X foci were monitored by immunocytochemistry.

RESULTS

The sequencing study identified a novel, potentially damaging missense mutation in a single patient. Silencing of did not significantly affect ATM kinase activity and did not impair the initial formation of γH2A.X foci, while we observed a marginally significant effect on residual γH2A.X foci at 6-48 h after IR.

CONCLUSIONS

does not harbor common mutations as BC susceptibility gene. Consistently, TPT1 protein is not required for the recognition of radiation-induced DNA damage via the ATM-dependent pathway and has only slight impact on timely repair. These results may be important when considering TPT1 as a DNA damage marker.