Radiation induces genomic instability and mammary ductal dysplasia in Atm heterozygous mice

Michael M. Weil, Frances S. Kittrell, Yongjia Yu, Maureen McCarthy, Ryan C. Zabriskie, Robert L. Ullrich

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Ataxia-telangiectasia (AT) is a genetic syndrome resulting from the inheritance of two defective copies of the ATM gene that includes among its stigmata radiosensitivity and cancer susceptibility. Epidemiological studies have demonstrated that although women with a single defective copy of ATM (AT heterozygotes) appear clinically normal, they may never the less have an increased relative risk of developing breast cancer. Whether they are at increased risk for radiation-induced breast cancer from medical exposures to ionizing radiation is unknown. We have used a murine model of AT to investigate the effect of a single defective Atm allele, the murine homologue of ATM, on the susceptibility of mammary epithelial cells to radiation-induced transformation. Here we report that mammary epithelial cells from irradiated mice with one copy of Atm truncated in the PI-3 kinase domain were susceptible to radiation-induced genomic instability and generated a 10% incidence of dysplastic mammary ducts when transplanted into syngenic recipients, whereas cells from Atm+/+ mice were stable and formed only normal ducts. Since radiation-induced ductal dysplasia is a precursor to mammary cancer, the results indicate that AT heterozygosity increases susceptibility to radiogenic breast cancer in this murine model system.

Original languageEnglish (US)
Pages (from-to)4409-4411
Number of pages3
JournalOncogene
Volume20
Issue number32
DOIs
StatePublished - Jul 19 2001

Fingerprint

Fibrocystic Breast Disease
Ataxia Telangiectasia
Genomic Instability
Radiation
Breast Neoplasms
Breast
Epithelial Cells
Radiation-Induced Neoplasms
Christianity
Radiation Tolerance
Heterozygote
Ionizing Radiation
Phosphatidylinositol 3-Kinases
Epidemiologic Studies
Alleles
Incidence
Genes
Neoplasms

Keywords

  • Ataxia-telangiectasia
  • Breast cancer
  • Genomic instability
  • Radiation effects

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Weil, M. M., Kittrell, F. S., Yu, Y., McCarthy, M., Zabriskie, R. C., & Ullrich, R. L. (2001). Radiation induces genomic instability and mammary ductal dysplasia in Atm heterozygous mice. Oncogene, 20(32), 4409-4411. https://doi.org/10.1038/sj.onc.1204589

Radiation induces genomic instability and mammary ductal dysplasia in Atm heterozygous mice. / Weil, Michael M.; Kittrell, Frances S.; Yu, Yongjia; McCarthy, Maureen; Zabriskie, Ryan C.; Ullrich, Robert L.

In: Oncogene, Vol. 20, No. 32, 19.07.2001, p. 4409-4411.

Research output: Contribution to journalArticle

Weil, MM, Kittrell, FS, Yu, Y, McCarthy, M, Zabriskie, RC & Ullrich, RL 2001, 'Radiation induces genomic instability and mammary ductal dysplasia in Atm heterozygous mice', Oncogene, vol. 20, no. 32, pp. 4409-4411. https://doi.org/10.1038/sj.onc.1204589
Weil, Michael M. ; Kittrell, Frances S. ; Yu, Yongjia ; McCarthy, Maureen ; Zabriskie, Ryan C. ; Ullrich, Robert L. / Radiation induces genomic instability and mammary ductal dysplasia in Atm heterozygous mice. In: Oncogene. 2001 ; Vol. 20, No. 32. pp. 4409-4411.
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