An Anti-Oncogenic Role for Decorin in Mammary Carcinoma
Abstract
A significant proportion of human breast cancers overexpress ErbB2, a member of the receptor tyrosine 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 demonstrated that decorin is a novel ligand for the EGFR. This interaction triggers a signaling cascade that leads to activation of MAP kinase and ultimately to growth suppression. In the preliminary data that support the basis of this proposal we discovered that decorin causes a functional inactivation of the oncogenic ErbB2 protein 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 demonstrate that transient transgene expression of decorin causes a significant growth inhibition of tumor xenografts. These cytostatic effects correlated with a reduced proliferative index and an attenuation of EGFR phosphorylation in vivo. Thus decorin gene therapy helps in retarding the growth of human tumors in immunocompromised animals and could represent a new independent or adjunctive therapeutic modality against cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2002
- Accession Number
- ADA411351
Entities
People
- Renato V. Iozzo
Organizations
- Thomas Jefferson University