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 Myc required for differentiation. 2) CREB/ATF1controls ING4 expression and differentiation, and the dynamics of CREB/ATF1 activation and its targets differ between normal and tumor cells. 3) Miz1 is an ING4 target required to suppress integrin 6 and 1 that is absent in tumor cells. 4) Erg negatively impacts differentiation, but only when expressed in the AR-positive cells. 5) Pten protein phosphatase activity sets the timing of differentiation, CREB/ATF1 activation, and induction of ING4. We identified targets of Myc, ING4, and CREB that can be used to screen human tissues proposed in Aim 3. We have met almost all of our first year objectives and extended into some of next years objectives.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2015
- Accession Number
- AD1000694
Entities
People
- Cynthia Miranti