Effect of HER-2/Neu Signaling on Sensitivity to TRAIL in Prostate Cancer
Abstract
The long-term goal of our research project is to develop a novel therapy for HER-2/neu overexpressing prostate cancer. Previous studies have shown that the HER-2/neu homodimer constitutively activates the PI(3)K-Akt-NF- B signal transduction pathway. During the research period, we examined whether the PI(3)K-Akt-NF- B signal transduction pathways are involved in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. As a first step we investigated whether modulation of the PI3K-Akt - NF- B signals affects TRAIL-induced cytotoxicity. We observed that acetyl salicylic acid (ASA: aspirin), amiloride, and quercetin inhibit the PI(3)K-Akt signal transduction pathway and promote TRAIL-induced cytotoxicity in HER-2/neu overexpressing human prostate cancer cells. The second step we examined how these chemical compounds enhances TRAIL cytotoxicity. We observed that ASA promotes TRAIL cytotoxicity by down-regulating SURVIVIN gene expression. We believe that the outcome of these studies provides information to support the development and clinical application of TRAIL for the treatment of HER-2/neu overexpressing human prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2007
- Accession Number
- ADA474604
Entities
People
- Yong J Lee
Organizations
- University of Pittsburgh