The Role of the Tyrosine Kinase JAK2 in the Development and Progression of Breast Cancer
Abstract
The purpose of this work is to assess the contribution of the tyrosine kinase Jak2 in the development and progression of breast cancer. To accomplish this, it is first necessary to define the role of Jak2 in normal mammary gland development. This is being investigated using two distinct approaches a) isolation of embryonic mammary glands from Jak2-null embryos and transplantation into the cleared fat pad of wild type mice and b) generation of a mammary-specific conditional knockout of the Jak2 gene. An analysis of mammary gland transplants has revealed an essential role for Jak2 in normal mammary epithelial development during pregnancy and lactation. Based on histology and marker expression, a secretory phenotype is not attained in the absence of Jak2. Furthermore, the epithelium maintains ductal-like features suggestive of a premature arrest in mammary cell proliferation and differentiation. Knowledge of the activation status of Jak2 in normal mammary gland and mammary tumors will help identify a key target for the development and testing of small molecule inhibitors (e.g. AG490) that specifically target the inhibition of Jak2 kinase activity and slow down tumor development and progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADA397620
Entities
People
- Hennighausen
- Jonathan M. Shillingford