Mouse Model of Human Breast Cancer Initiated by a Fusion Oncogene
Abstract
In this study, we generated a novel mouse model of human breast cancer based on a recurrent chromosomal translocation that produces the TEL-NTRK3 fusion oncogene, as the initiating mutation in human secretory breast carcinoma. In this model, we created a Ore-lox conditional knockin allele (TN) to express the TN fusion protein from the endogenous Tel locus in a tissue-specific manner. When TN is activated in mammary glands by whey acidic protein (WAP) promoter-driven Ore, all female mice exhibit extensive lobuloalveolar hyperplasia and develop multifocal mammary tumors as early as 4-month of age. Using the Ore-lox genetic marking approach coupled with a conditional Rosa26-lacZ reporter, we identified putative target cells of TN, a population of transient mammary epithelial cells (MECs) that appear only during estrus in wild type virgin females, but become premalignant hyerplastic MECs once TN is activated by WAP-Ore. Additional genetic/epigenetic changes may eventually convert them to cancer. Thus, our model is useful for studying target cells of breast cancer and provides a preclinical system for testing novel therapies for breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2006
- Accession Number
- ADA459723
Entities
People
- Stuart H. Orkin