Apoptosis Induction by Targeting Interferon Gamma Receptor 2 (IFNgammaR2) in Prostate Cancer: Ligand (IFNgamma)-Independent Novel Function of IFNgammaR2 as a Bax Inhibitor
Abstract
In our preliminary study, we found that IFNgammaR2 has previously unknown function as an inhibitor of Bax. Bax is a key mediator of apoptosis. We found that IFNgammaR2 is overexpressed in prostate cancer, and we hypothesize that abnormally high level of IFNgammaR2 confers apoptosis resistance of prostate cancer. In this project, we will investigate the role of IFNgammaR2 in drug resistance of prostate cancer and explore the development of strategies that can activate Bax-induced apoptosis in prostate cancer by inactivating IFNgammaR2. In Year 3, we planned to determine what kind of cell type(s) in prostate cancer tissue expresses IFNgammaR2 by performing immunohistochemistry. Another important proposed experiment is to determine whether IFNgammaR2 expression profile (expression levels and expression type (cytosol or membrane expression, or cell type specific staining) can be used as a biomarker to predict the clinical outcome. In this report, we show that IFNgammaR2 is expressed in a particular group of basal cells in prostate of patients who had recurrence. IFNgammaR2 positive cells were not detected in luminal cells or luminal cell type cancer cells. Using prostate cancer cell lines, we found that IFNgammaR2 expression increases according to the progression of malignancy, i.e. from androgen-dependent state to androgen-independent and metastatic state. These results suggest that elevation of IFNgammaR2 expression is correlated with progression of prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2015
- Accession Number
- ADA623598
Entities
People
- Shigemi Matsuyama
Organizations
- Case Western Reserve University