bcr661 BCJ Oral presentation <p>Estrogen receptor alpha-positive and negative mouse mammary tumors through somatic mutations of <it>p53 </it>in mammary carcinogenesis</p> Lin S-CJ Lee K-F Nikitin AY Bushnell KM Hilsenbeck SG Cardiff RD Li A Kang K-W Frank SA Lee W-H Lee EY-HP

Department of Developmental and Cell Biology and Department of Biological Chemistry, University of California, Irvine, California, USA

The Salk Institute for Biological Studies, La Jolla, California, USA

Department of Biomedical Sciences, Cornell University, Ithaca, New York, USA

Institute of Biotechnology, Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

Department of Medicine and Department of Molecular and Cellular Biology, Breast Center, Baylor College of Medicine, Houston, Texas, USA

Center for Comparative Medicine, University of California, Davis, California, USA

Department of Ecology and Evolutionary Biology, University of California, Irvine, California, USA

 Breast Cancer Res <p>24<sup>th </sup>Congress of the International Association for Breast Cancer Research. Advances in human breast cancer research: preclinical models</p> Meeting abstracts <p>24<sup>th </sup>Congress of the International Association for Breast Cancer Research. Advances in human breast cancer research: preclinical models</p> Sacramento, USA 1-5 November 2003 1465-5411 2003 5 Suppl 1 2 10.1186/bcr661 31 10 2003

Approximately 70% of human breast cancers are estrogen receptor alpha (ERα)-positive, but the origins of ERα-positive and ERα-negativetumors remain unclear. Most mouse models produce only ERα-negative tumors. In addition, these mouse tumors metastasize at a low rate relative to human breast tumors. We report that somatic mutations of p53 in mouse mammary epithelial cells lead to ERα-positive and ERα-negative tumors. p53 inactivation in pre-pubertal/pubertal mice, but not in adult mice, leads to the development of ERα-positive tumors, suggesting that developmental stages influence the availability of ERα-positive tumor origin cells. These tumors have a high rate of metastasis that is independent of tumor latency. An inverse relationship between the number of targeted cells and median tumor latency was also observed. The median tumor latency reaches a plateau when targeted cell numbers exceed 20%, implying the existence of saturation kinetics for breast carcinogenesis. Genetic alterations commonly observed in human breast cancer including c-myc amplification and Her2/Neu/erbB2 activation were seen in these mouse tumors. Since it is feasible to isolate ERα-positive epithelial cells from normal mammary glands and tumors, molecular mechanisms underlying ERα-positive and ERα-negative mammary carcinogenesis can be systematically addressed using this model.