{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T05:28:33Z","timestamp":1791005313084,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"2-3","license":[{"start":{"date-parts":[[2002,3,7]],"date-time":"2002-03-07T00:00:00Z","timestamp":1015459200000},"content-version":"vor","delay-in-days":65,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2002,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>BRCA1<\/jats:italic> is the first breast cancer\u2013associated gene, whose mutation predisposes women to breast and ovarian cancers. Targeted mutations of <jats:italic>Brca1<\/jats:italic> in the mouse result in embryonic lethality primarily attributed to cellular proliferation defects, raising questions about the mechanisms by which <jats:italic>Brca1<\/jats:italic> represses tumor formation. To overcome the early lethality, we engineered <jats:italic>Brca1<\/jats:italic> by flanking its exon 11 with loxP sites. We showed that deletion of the exon by <jats:italic>EIIA\u2010Cre,<\/jats:italic> which expresses Cre in the germline, causes <jats:italic>p53<\/jats:italic>\u2010dependent lethality at late gestation. On the other hand, <jats:italic>MMTV\u2010Cre,<\/jats:italic> which expresses Cre in mammary epithelium, resulted in tumorigenesis at low frequency after a long latency, accompanied by increased epithelial cell apoptosis and abnormal ductal development. Mammary tumor formation was significantly accelerated in a <jats:italic>p53<\/jats:italic><jats:sup><jats:italic>+\/<\/jats:italic>\u2212<\/jats:sup> genetic background; however, it still appeared in a stochastic fashion, suggesting the involvement of additional factors. Notably, the tumors were highly diverse in histopathology and displayed extensive genetic\/molecular alterations, including overexpression of ErbB2, <jats:italic>c\u2010Myc<\/jats:italic>, <jats:italic>p27<\/jats:italic>, and Cyclin D1, and downregulation of <jats:italic>p16<\/jats:italic> in the majority of tumors. This observation suggests roles for these proteins in <jats:italic>Brca1<\/jats:italic>\u2010associated tumorigenesis. Environ. Mol. Mutagen. 39:171\u2013177, 2002. 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