ATM induction insufficiency in a radiosensitive breast-cancer patient.
The ataxia telangiectasia (A-T) gene (ATM) is a dominant breast cancer gene with tumour suppressor activity. ATM also regulates cellular sensitivity to ionising radiation (IR) presumably through its role as a facilitator of DNA repair. In normal cells and tissues the ATM protein is rapidly induced by IR to threshold/maximum levels. The kinase function of the ATM protein is also rapidly activated in response to IR. The fact that women carriers of ATM mutations can have an increased risk of developing breast cancer and that many sporadic breast tumours have reduced levels of the ATM protein broadens the scope of ATM's tumour suppressor within the breast. This report describes the downregulation of ATM protein levels in a radiosensitive breast cancer patient. Postinduction ATM levels were up to tenfold lower in the patient's fresh tissues compared to normal controls. These results might indicate a much broader role for ATM anomalies in breast cancer aetiology.
Molecular Genetics Laboratories, Cancer Care Center, Division of Cancer Services, The St George Hospital and University of New South Wales, Australia. r.clarke@unsw.edu.au
R A
RA
Clarke
Z H
ZH
Fang
P J
PJ
Marr
C S
CS
Lee
J H
JH
Kearsley
G
G
Papadatos
D001260:Ataxia Telangiectasia / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000532:radiotherapy*; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011836:Radiation Tolerance; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases