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.