An Anti-Oncogenic Role for Decorin in Mammary Carcinoma
Abstract
A significant proportion of human breast cancers overexpress ErbB2, a member of the receptor tyronsine kinase gene family that also includes the epidermal growth factor receptor (EGFR). Overexpression of ErbB2 correlates with increased metastatic potential and poorer prognosis. Agents that antagonize the activity of ErbB family members have obvious clinical implications. We have previously discovered that decorin causes a functional inactivation of the oncogenic ErbB2 in mammary carcinoma cells overexpressing ErbB2. This leads to growth inhibition and cytodifferentiation of mammary tumor cells and a concurrent suppression of their tumorigenic potential in vivo. We have successfully demonstrated decorin's cytostatic effect both in vitro and in vivo with a metastatic breast cancer cell model. Thus, decorin gene therapy helps in retarding the growth of human tumors in immunocompromised animals and could represent a new independent or adjuctive therapeutic modality against cancer. We have additionally created a breast cancer cell line that contains the decorin transgene under the control of an inducible promoter. We plan on using this cell line to study decorin's temporal effects on both primary tumor development as well as on tumor spread and metastases. Our ultimate goal is to prove decorin's efficacy as a tumor suppressor and possible means of therapy fir breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2003
- Accession Number
- ADA423067
Entities
People
- Renato V. Iozzo
Organizations
- Thomas Jefferson University