{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T17:08:39Z","timestamp":1760980119584},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2004,12,10]],"date-time":"2004-12-10T00:00:00Z","timestamp":1102636800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2004,12,10]],"date-time":"2004-12-10T00:00:00Z","timestamp":1102636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Breast Cancer Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p>Ataxia-telangiectasia is an autosomal-recessive disease that affects neuro-immunological functions, associated with increased susceptibility to malignancy, chromosomal instability and hypersensitivity to ionizing radiation. Although ataxia-telangiectasia mutated (<jats:italic>ATM<\/jats:italic>) heterozygous deficiency has been proposed to increase susceptibility to breast cancer, some studies have not found excess risk. In experimental animals, increased susceptibility to breast cancer is not observed in the <jats:italic>Atm<\/jats:italic> heterozygous deficient mice (<jats:italic>Atm<\/jats:italic><jats:sup>+\/-<\/jats:sup>) carrying a knockout null allele. In order to determine the effect of <jats:italic>Atm<\/jats:italic> heterozygous deficiency on mammary tumourigenesis, we generated a series of <jats:italic>Atm<\/jats:italic><jats:sup>+\/-<\/jats:sup> mice on the <jats:italic>p53<\/jats:italic><jats:sup>+\/-<\/jats:sup> background with a certain predisposition to spontaneous development of mammary carcinomas, and we examined the development of the tumours after X-irradiation.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>BALB\/cHeA-<jats:italic>p53<\/jats:italic><jats:sup>+\/-<\/jats:sup> mice were crossed with MSM\/Ms-<jats:italic>Atm<\/jats:italic><jats:sup>+\/-<\/jats:sup> mice, and females of the F<jats:sub>1<\/jats:sub> progeny ([BALB\/cHeA \u00d7 MSM\/Ms]F<jats:sub>1<\/jats:sub>) with four genotypes were used in the experiments. The mice were exposed to X-rays (5 Gy; 0.5 Gy\/min) at age 5 weeks.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>We tested the effect of haploinsufficiency of the <jats:italic>Atm<\/jats:italic> gene on mammary tumourigenesis after X-irradiation in the <jats:italic>p53<\/jats:italic><jats:sup>+\/-<\/jats:sup> mice of the BALB\/cHeA \u00d7 MSM\/Ms background. The singly heterozygous <jats:italic>p53<\/jats:italic><jats:sup>+\/-<\/jats:sup> mice subjected to X-irradiation developed mammary carcinomas at around 25 weeks of age, and the final incidence of mammary carcinomas at 39 weeks was 31% (19 out of 61). The introduction of the heterozygous <jats:italic>Atm<\/jats:italic> knockout alleles into the background of the <jats:italic>p53<\/jats:italic><jats:sup>+\/-<\/jats:sup> genotype significantly increased the incidence of mammary carcinoma to 58% (32 out of 55) and increased the average number of mammary carcinomas per mouse. However, introduction of <jats:italic>Atm<\/jats:italic> alleles did not change the latency of development of mammary carcinoma.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusion<\/jats:title>\n                        <jats:p>Our results indicate a strong enhancement in mammary carcinogenesis by <jats:italic>Atm<\/jats:italic> heterozygous deficiency in <jats:italic>p53<\/jats:italic><jats:sup>+\/-<\/jats:sup> mice. Thus, doubly heterozygous mice represent a useful model system with which to analyze the interaction of heterozygous genotypes for <jats:italic>p53<\/jats:italic>, <jats:italic>Atm<\/jats:italic> and other genes, and their effects on mammary carcinogenesis.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/bcr968","type":"journal-article","created":{"date-parts":[[2005,1,12]],"date-time":"2005-01-12T14:12:38Z","timestamp":1105539158000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Atm heterozygous deficiency enhances development of mammary carcinomas in p53heterozygous knockout mice"],"prefix":"10.1186","volume":"7","author":[{"given":"Seiichi","family":"Umesako","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kae","family":"Fujisawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayoko","family":"Iiga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuko","family":"Mori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doo-Pyo","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang-Woo","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satomi","family":"Haga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syunsuke","family":"Imai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Otsura","family":"Niwa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaaki","family":"Okumoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2004,12,10]]},"reference":[{"key":"967_CR1","first-page":"347","volume-title":"In Handbook of Clinical Neurology","author":"R Sedgewick","year":"1991","unstructured":"Sedgewick R, Boder E: Ataxia-telangiectasia. 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