Accession Number:

ADA459723

Title:

Mouse Model of Human Breast Cancer Initiated by a Fusion Oncogene

Descriptive Note:

Final rept. 15 Aug 2005-14 Aug 2006

Corporate Author:

CHILDREN'S HOSPITAL CORP BOSTON MA

Personal Author(s):

Report Date:

2006-09-01

Pagination or Media Count:

14.0

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 geneticepigenetic 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.

Subject Categories:

  • Genetic Engineering and Molecular Biology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE