ING4 Loss in Prostate Cancer Progression
Technical Report,23 Sep 2015,22 Sep 2016
Van Andel Research Institute Grand Rapids United States
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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 CREBATF1 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.
- Medicine and Medical Research