Novel Growth Factor as Prognostic Marker for Estrogen-Independence in Breast Cancer
Abstract
The Concept Award focused on investigating the expression on the biomarker PCDGF/GP88 in breast cancer and its effect on the acquisition of estrogen independence and tamoxifen resistance, a hallmark of breast cancer with poor prognosis. Specific aims set for this application were achieved. PCDGF expression was examined by immunohistochemistry in paraffin embedded breast cancer biopsies. A study with 206 samples showed that PCDGF was mostly negative in benign lesions. In contrast 67% of ductal carcinoma in situ (ICIS) and 80% of invasive ductal carcinoma (IDC) stained positive for PCDGF/GP88. In IDcs, PCDGF expression correlated with tumor grade, p53 and Ki67. In contrast, no correlation was found with ER/PR and Her-2 expression. Based on these results, we examined the effect of increased expression of PCDGF in ER+MCF-7 cell line as model system. We showed that increased of PCDGF expression in these cells led to estrogen independence and to resistance to the antiestrogen tamoxifen both in vitro and in vivo in mouse xenografts. Molecular studies demonstrated that PCDGF exerts its effect by blocking the apoptotic effect of tamoxifen. These data demonstrate the importance of PCDGF/GP88 as a novel target for the development of therapy for tamoxifen resistant breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2003
- Accession Number
- ADA424094
Entities
People
- Ginette Serrero
Organizations
- University of Maryland, Baltimore