Radiation induces genomic instability and mammary ductal dysplasia in Atm heterozygous mice.
Oncogene
; 20(32): 4409-11, 2001 Jul 19.
Article
em En
| MEDLINE
| ID: mdl-11466622
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Radiação Ionizante
/
Neoplasias da Mama
/
Proteínas Serina-Treonina Quinases
/
Carcinoma Intraductal não Infiltrante
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Oncogene
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos