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(American Journal of Pathology. 2003;163:1713-1719.)
© 2003 American Society for Investigative Pathology

Short Communication

Introduction of Estrogen Receptor- into the tTA/TAg Conditional Mouse Model Precipitates the Development of Estrogen-Responsive Mammary Adenocarcinoma

Maddalena T. Tilli^*, M. Silvina Frech, Mary E. Steed, Kathleen S. Hruska, Michael D. Johnson, Jodi A. Flaws and Priscilla A. Furth^*

From the Program in Human Genetics^* and the Department of Epidemiology and Preventive Medicine, School of Medicine, University of Maryland, Baltimore, Baltimore, Maryland; the Department of Oncology, Lombardi Cancer Center, Georgetown University, Washington, District of Columbia; and the Gene Evaluation and Mapping Laboratory, Agricultural Research Service, Animal and Natural Resources Institute, Beltsville Agricultural Research Center, United States Department of Agriculture, Beltsville, Maryland

Conditional expression of estrogen receptor (ER)-) was introduced into tetracycline-responsive MMTV-tTA/tetop-TAg mice to develop a mouse model of estrogen-responsive ER--positive mammary adenocarcinoma. Mammary adenocarcinomas developed in the mice with a mean latency of 11 months. Precursor lesions including ductal hyperplasia and hyperplastic alveolar nodules were present by the age of 4 months. The mammary adenocarcinomas exhibited histological features similar to human breast cancers. ER steroid-binding studies conducted on adenocarcinoma lysates demonstrated binding to estradiol. Tumor explant studies in the presence and absence of estradiol in ovariectomized athymic nude mice revealed that growth of mammary tumors was stimulated by estrogen. In addition, the presence of ER- altered the tumor spectrum in other MMTV-targeted tissues in the tTA/TAg female mice. Lymphomas, which develop in 40% of tTA/TAg female mice, were found in only 4% of tTA/TAg/ER- mice (P = 0.014, chi-square test). These experiments demonstrate that the introduction of an ER- transgene targeted to mammary epithelial cells can be used to develop mouse models of ER--responsive mammary cancer.

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