Elevation of the chromatin repression factor enhancer of zeste homolog (EZH2) is associated with progression and poor prognosis in several human cancers including prostate cancer.
However, the mechanisms driving EZH2 expression are not fully understood. In this study, we investigated the functional synergy in prostate cancers in mice resulting from activation of the androgen receptor, Kras, and Akt, which drives three of the most frequently activated oncogenic signaling pathways in prostate cancer. Although, any two of these three events were sufficient to promote the formation and progression of prostate cancer, only the synergy of androgen receptor and Kras signaling could elevate EZH2 expression and expand prostate cancer progenitor cells in vivo. Our findings have revealed a genetic mechanism resulting in enhanced EZH2 expression during the progression of aggressive prostate cancer, with important implications for understanding how to target advanced disease where cancer progenitor cells may be critical.
Written by:
Cai H, Memarzadeh S, Stoyanova T, Beharry Z, Kraft AS, Witte ON. Are you the author?
Hollings Cancer Center and Department of Medicine, Department of Pharmaceutical and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina; Department of Obstetrics and Gynecology, David Geffen School of Medicine; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research; Department of Microbiology, Immunology, and Molecular Genetics, University of California; and Howard Hughes Medical Institute, University of California Los Angeles, Los Angeles, California.
Reference: Cancer Res. 2012 Sep 15;72(18):4672-4681.
doi: 10.1158/0008-5472.CAN-12-0228
PubMed Abstract
PMID: 22805308
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