title: ATM protein synthesis patterns in sporadic breast cancer.
abstract: OBJECTIVE
  The gene mutated in ataxia-telangiectasia (A-T), designated ATM (for "A-T mutated"), is believed to be associated with an increased risk of developing breast cancer. Most patients with A-T have null mutations of the ATM gene that appear to give rise to a truncated nonfunctional ATM protein. Therefore, the increased risk of breast cancer reported in A-T heterozygotes appears to be the result of haplo-insufficiency of ATM in breast tissues. This study aimed to determine whether reduced synthesis of ATM was also an important factor in sporadic breast cancer.
  
  
  METHODS
  Paraffin wax embedded tissues from patients with breast invasive ductal carcinoma (IDC) (n = 42), patients with ductal carcinoma in situ (DCIS) (n = 17), and others with lymph node metastases (n = 14) were studied. A streptavidin-biotin-peroxidase system was used to stain tissue sections for the ATM protein using the ATM-4BA and CT-1 polyclonal and monoclonal antibodies, respectively. The protein truncation test was used to screen for mutations in the ATM gene in those patients who had greatly reduced ATM protein immunoreactivity in the primary carcinoma (n = 3).
  
  
  RESULTS
  Most metastatic breast carcinomas in lymph nodes (71%) had greatly reduced or absent ATM protein synthesis, which was significant when compared with that observed in non-metastatic invasive breast carcinomas (p = 0.029; chi 2 test). Although not significant (p = 0.045; chi 2 test), some sporadic breast carcinomas (14 of 42) also had reduced or absent ATM protein immunoreactivity. The protein truncation test did not reveal any gross ATM gene abnormality in the cases tested, indicating that the patients were not A-T heterozygotes, who are predisposed to breast cancer.
  
  
  CONCLUSIONS
  A reduction in immunohistochemically detectable ATM protein in sporadic breast carcinoma implicates ATM in the progression of the disease.
authors.affiliation: Division of Cancer Services, St George Hospital, Kogarah, NSW, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Kairouz
authors.forename: R A
authors.initials: RA
authors.lastname: Clarke
authors.forename: P J
authors.initials: PJ
authors.lastname: Marr
authors.forename: D
authors.initials: D
authors.lastname: Watters
authors.forename: M F
authors.initials: MF
authors.lastname: Lavin
authors.forename: J H
authors.initials: JH
authors.lastname: Kearsley
authors.forename: C S
authors.initials: CS
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism*; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases