ING4 Loss in Prostate Cancer Progression
Abstract
The goal of this project is to identify specific differentiation events whose disruption by Myc and Pten leads to aggressive PCa. Our Aims are to 1) determine how ING4 controls prostate epithelial differentiation; 2) determine how loss of ING4 impacts tumorigenesis; and 3) determine how loss of ING4 in patients relates to tumor progression. We found the following: 1) Notch3 is a target of p38MAPK and Myc signaling required for differentiation. 2) CREB1 and ATF1 differentially control ING4 expression during differentiation, and aberrant CREB/ATF1 activation in tumor cells prevents ING4 expression and differentiation. 3) Miz1 is an ING4 target that enhances differentiation that is absent in tumor cells. 4) JFK is an ING4 target that suppresses ING4 expression through ubquitination. 5) Erg negatively impacts differentiation, but only when expressed in the AR-positive cells. We have identified targets of Myc, ING4, and CREB that can be used to screen human tissues proposed in Aim 3 to identify aggressive tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2016
- Accession Number
- AD1033179
Entities
People
- Cynthia Miranti