Expression of the ATM gene is significantly reduced in sporadic breast carcinomas.
The gene mutated in ataxia telangiectasia (A-T) patients (ATM) is located on chromosome 11q22-23, a region frequently altered in mammary tumors. Patients homozygous for ATM mutations are prone to develop a variety of different neoplasms. Female heterozygotes have been reported to carry a 5- to 8-fold increased risk of breast cancer. However, germline mutations in the ATM gene are rare in women with sporadic breast carcinomas. Most of the alterations described in A-T patients result in a functionally inactive ATM protein. Moreover, it has been suggested that mutations of the ATM gene in A-T patients influence the amount of ATM mRNA and that this may affect the severity of the disease. In the present study, we have analyzed ATM transcripts in a series of 39 breast carcinomas, 14 benign breast lesions and 12 normal breast tissue samples. ATM mRNA levels were determined by semiquantitative competitive RT-PCR. Competitor RNA molecules for the ATM gene and the housekeeping gene beta-2-microglobulin (B2M) were generated by PCR mutagenesis. Low concentrations of ATM transcripts were detected in breast carcinomas, intermediate levels in benign lesions and highest levels in normal breast tissue specimens (F-test, p = 0.0013). Our results indicate that reduced expression of the ATM gene may contribute to the development and/or malignant progression of breast carcinomas.
Waha
A
A
Department of Neuropathology, University of Bonn Medical Center, Germany.
Sturne
C
C
Kessler
A
A
Koch
A
A
Kreyer
E
E
Fimmers
R
R
Wiestler
O D
OD
von Deimling
A
A
Krebs
D
D
Schmutzler
R K
RK
D064007:Ataxia Telangiectasia Mutated Proteins; D001940:Breast / Q000378:metabolism*; D001941:Breast Diseases / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D018797:Cell Cycle Proteins; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D004252:DNA Mutational Analysis; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins; D005260:Female; D005819:Genetic Markers; D006801:Humans; D016350:Leucine Zippers; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D009361:Neoplasm Invasiveness; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D017931:DNA Primers; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D011506:Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases