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, whose interaction with EGFR/ErbB family members ultimately leads to significant 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. In this final report, we demonstrate that transient transgene expression of decorin delivered by an adenoviral vector causes a significant growth inhibition of multiple tumor xenografts. These cytostatic effects correlated with a reduced proliferative index and an attenuation of EGFR phosphorylation in vivo. Further, direct treatment of metastatic tumors with decorin protein can abrogate spreading, as can expression of decorin in an inducible cell system. The effects clearly demonstrate decorin's effectiveness in not only suppressing primary tumor growth, but also metastatic spread via it interaction with ErbB family members.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2004
- Accession Number
- ADA431185
Entities
People
- Renato V. Iozzo
Organizations
- Thomas Jefferson University