Mouse Model of Human Breast Cancer Initiated by a Fusion Oncogene

reportActive / Technical Report | Accession Number: ADA459723 | Open PDF

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.

Author(s):
Orkin, Stuart H.
Author Organization(s):
CHILDREN'S HOSPITAL CORP BOSTON MA
Descriptive Note:
Final rept. 15 Aug 2005-14 Aug 2006
Supplementary Note:
The original document contains color images.
Pagination:
0014

Security Markings

DOCUMENT & CONTEXTUAL SUMMARY

Distribution:
Approved For Public Release
Distribution Statement:
Approved For Public Release; Distribution Is Unlimited.

RECORD

Collection: TR
Identifying Numbers
Contract/Grant Number(s):
W81XWH-05-1-0502
Monitor Series:
USAMRMC
 Subject Terms
Joint Capability Areas:
JCA_5_Command and Control; JCA_5.3_Planning
Communities of Interest:
No COI(s) Identified
Descriptor(s):
*TISSUES(BIOLOGY), *CHROMOSOMES, *GENES, *BREAST CANCER, *CELLS(BIOLOGY), TRANSIENTS, MICE, FEMALES, ANATOMICAL MODELS, TRANSLOCATION, ONCOGENESIS, SECRETION, MAMMARY GLANDS, GENETICS, GENETIC ENGINEERING, CLINICAL MEDICINE, MUTATIONS, EPITHELIUM
Field(s)/Group(s):
Genetic Engineering and Molecular Biology, Medicine and Medical Research
Keyword(s):
CHROMOSOMAL TRANSLOCATION, GENE TARGETING, MOUSE MODELS, LOBULOALVEOLAR HYPERPLASIA, TN(KNOCKIN ALLELE), *FUSION ONCOGENES
Report Date:
2006 Sep 01
Creation Date:
2007 Jan 17