Lack of defective expression of the ATM gene in sporadic breast cancer tissues and cell lines.

  • Authors:
    • S Kovalev
    • A Mateen
    • A I Zaika
    • B J O'Hea
    • U M Moll
  • View Affiliations

  • Published online on: April 1, 2000     https://doi.org/10.3892/ijo.16.4.825
  • Pages:825-856
Metrics: HTML 0 views | PDF 0 views     Cited By (CrossRef): 0 citations

Abstract

Homozygous mutations of the gene mutated in ataxia telangiectasia (ATM) causes the AT syndrome, a pleiotropic phenotype that includes an increased risk of cancer. Most of the known mutations at the ATM gene lead to truncations which are usually associated with instability of mRNA and protein. A decrease or loss of ATM protein expression is associated with specific lymphoid malignancies in AT and non-AT patients. ATM is located within a region in chromosome 11q22-23 that is frequently undergoing loss of heterozygosity in sporadic breast cancer. Epidemiological studies estimated a 4-fold increase in breast cancer risk in heterozygous women. However, direct mutational analysis failed to clearly support a role for mutant ATM alleles in breast carcinogenesis. If ATM does have a suppressor role in this tissue, one would expect deficient ATM expression. We therefore tested the hypothesis that the expression of the ATM gene is reduced in sporadic breast cancer. We determined ATM transcript levels using competitive RT-PCR on 89 randomly selected sporadic breast cancer samples and 29 normal breast tissues. Of these, 11 were matched normal/cancer pairs. We also evaluated 7 breast cancer cell lines. Deficiency in ATM expression was not observed. Of the 11 matched pairs, 7 tumors expressed mildly higher levels, 3 tumors expressed the same amount and only 1 tumor expressed <50% of the normal match. In addition, 3 cancers with tumor-associated LOH of the ATM gene expressed higher mRNA levels in the tumors than in their normal tissue matches, suggesting that no correlation exists between tumors with LOH and decreased ATM expression. In summary, our results do not support a suppressor role for ATM in the development of sporadic breast cancer.

Related Articles

Journal Cover

April 2000
Volume 16 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2016 Impact Factor: 3.079
Ranked #33/217 Oncology
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Kovalev, S., Mateen, A., Zaika, A., O'Hea, B., & Moll, U. (2000). Lack of defective expression of the ATM gene in sporadic breast cancer tissues and cell lines.. International Journal of Oncology, 16, 825-856. https://doi.org/10.3892/ijo.16.4.825
MLA
Kovalev, S., Mateen, A., Zaika, A., O'Hea, B., Moll, U."Lack of defective expression of the ATM gene in sporadic breast cancer tissues and cell lines.". International Journal of Oncology 16.4 (2000): 825-856.
Chicago
Kovalev, S., Mateen, A., Zaika, A., O'Hea, B., Moll, U."Lack of defective expression of the ATM gene in sporadic breast cancer tissues and cell lines.". International Journal of Oncology 16, no. 4 (2000): 825-856. https://doi.org/10.3892/ijo.16.4.825