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

Clinical and Translational Radiation Oncology
Katharina NeuhäuserNatalia Bogdanova

Abstract

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. The TPT1 coding sequence was scanned for mutations in genomic DNA from 200 breast cancer patients. TPT1 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. The sequencing study identified a novel, potentially damaging missense mutation in a single patient. Silencing of TPT1 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. TPT1 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.

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Methods Mentioned

BETA
genotyping
transfection
X-ray
confocal microscopy
nuclear translocation

Software Mentioned

analysis
MutationTaster
PhyloP
GraphPad Prism
GraphPad
MaxEntScan
SIFT
Image J
Polyphen
ESEfinder

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