Expression patterns of the ATM gene in mammary tissues and their associations with breast cancer survival.
BACKGROUND
The ataxia-telangiectasia mutated (ATM) gene plays a critical role in cell-cycle arrest, apoptosis, and DNA repair. However, to date, no study has directly investigated the association between ATM gene expression and breast cancer survival.


METHODS
ATM gene expression levels were evaluated in tumor and adjacent normal tissue from patients diagnosed with primary breast cancer or BBD using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) assays. Cox regression models were used to evaluate the association of ATM gene expression and survival in a cohort of 471 breast cancer patients.


RESULTS
In breast cancer cases, ATM expression in cancer tissues was decreased by approximately 50% compared with adjacent normal tissues from the same patients. In BBD cases, the expression level of the ATM gene was similar in benign tumor tissue and adjacent normal tissues. No apparent difference was found in ATM gene expression levels in adjacent normal tissues obtained from cancer patients or BBD controls. Compared with patients with the lowest tertile of the ATM mRNA, patients in the upper 2 tertiles had more favorable disease-free survival (hazard ratio [HR]=0.46, 95% confidence interval [CI]: 0.30-0.73 and HR=0.52, 95% CI: 0.33-0.81, respectively) and overall survival (HR=0.56, 95% CI: 0.35-0.92 and HR=0.70, 95% CI: 0.43-1.13, respectively).


CONCLUSIONS
The ATM gene expression was down-regulated in breast cancer tissues and a high ATM gene expression level in breast cancer tissue was associated with a favorable prognosis.
Ye
Chuanzhong
C
Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt Ingram-Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2587, USA.
Cai
Qiuyin
Q
Dai
Qi
Q
Shu
Xiao-ou
XO
Shin
Aesun
A
Gao
Yu-Tang
YT
Zheng
Wei
W
D000328:Adult; D064007:Ataxia Telangiectasia Mutated Proteins; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality*; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D042361:Mammary Glands, Human / Q000378:metabolism*; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases