ATM has a major role in the double-strand break repair pathway dysregulation in sporadic breast carcinomas and is an independent prognostic marker at both mRNA and protein levels

British Journal of Cancer
S RondeauI Bièche

Abstract

Ataxia telangiectasia mutated (ATM) is a kinase that has a central role in the maintenance of genomic integrity by activating cell cycle checkpoints and promoting repair of DNA double-strand breaks (DSB). In breast cancer, a low level of ATM was correlated with poor outcome; however, the molecular mechanism of this downregulation is still unclear. We used qRT-PCR assay to quantify mRNA levels of ATM gene in 454 breast tumours from patients with known clinical/pathological status and outcome; reverse phase protein arrays (RPPA) were used to assess the levels of ATM and 14 proteins in 233 breast tumours. ATM mRNA was associated with poor metastasis-free survival (MFS) (P=0.00012) on univariate analysis. ATM mRNA and protein levels were positively correlated (P=0.00040). A low level of ATM protein was correlated with poorer MFS (P=0.000025). ATM expression at mRNA or protein levels are independent prognostic factors on multivariate analysis (P=0.00046 and P=0.00037, respectively). The ATM protein level was positively correlated with the levels of six proteins of the DSB repair pathway: H2AX (P<0.0000001), XRCC5 (P<0.0000001), NBN (P<0.0000001), Mre11 (P=0.0000029), Rad50 (P=0.0064), and TP53BP1 (P=0.026), but not with proteins inv...Continue Reading

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Feb 13, 2016·British Journal of Cancer·Maria E LomakinaAlexis Gautreau
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Methods Mentioned

BETA
reverse-transcription PCR
electrophoresis
PCR
protein array

Software Mentioned

PE Biosystems
MicroVigene
Oligo
Normacurve

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