PMID: 11921186Mar 29, 2002Paper

Tumor formation in Brca1 conditional mutant mice

Environmental and Molecular Mutagenesis
Chu-Xia Deng

Abstract

BRCA1 is the first breast cancer-associated gene, whose mutation predisposes women to breast and ovarian cancers. Targeted mutations of Brca1 in the mouse result in embryonic lethality primarily attributed to cellular proliferation defects, raising questions about the mechanisms by which Brca1 represses tumor formation. To overcome the early lethality, we engineered Brca1 by flanking its exon 11 with loxP sites. We showed that deletion of the exon by EIIA-Cre, which expresses Cre in the germline, causes p53-dependent lethality at late gestation. On the other hand, MMTV-Cre, 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 p53(+/-) 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, c-Myc, p27, and Cyclin D1, and downregulation of p16 in the majority of tumors. This observation suggests roles for these proteins in Br...Continue Reading

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Citations

Sep 6, 2002·Oncogene·M Christine Hollander, Albert J Fornace
Aug 15, 2012·The Journal of Obstetrics and Gynaecology Research·Masayuki SekineKenichi Tanaka
Nov 26, 2002·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·N AuerspergG W E Mitchell
Sep 8, 2010·Cell Research·Vivek ShuklaChu-Xia Deng
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Jan 5, 2011·Protein & Cell·Jiaxue WuXiaochun Yu
Nov 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Rui-Hong WangChu-Xia Deng
Oct 25, 2012·Cancer Metastasis Reviews·Jennifer Dine, Chu-Xia Deng
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Dec 3, 2014·Cold Spring Harbor Protocols·Chu-Xia Deng

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