Publication Date:
2012-12-15
Description:
Epigenetic regulators represent a promising new class of therapeutic targets for cancer. Enhancer of zeste homolog 2 (EZH2), a subunit of Polycomb repressive complex 2 (PRC2), silences gene expression via its histone methyltransferase activity. We found that the oncogenic function of EZH2 in cells of castration-resistant prostate cancer is independent of its role as a transcriptional repressor. Instead, it involves the ability of EZH2 to act as a coactivator for critical transcription factors including the androgen receptor. This functional switch is dependent on phosphorylation of EZH2 and requires an intact methyltransferase domain. Hence, targeting the non-PRC2 function of EZH2 may have therapeutic efficacy for treating metastatic, hormone-refractory prostate cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625962/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625962/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Kexin -- Wu, Zhenhua Jeremy -- Groner, Anna C -- He, Housheng Hansen -- Cai, Changmeng -- Lis, Rosina T -- Wu, Xiaoqiu -- Stack, Edward C -- Loda, Massimo -- Liu, Tao -- Xu, Han -- Cato, Laura -- Thornton, James E -- Gregory, Richard I -- Morrissey, Colm -- Vessella, Robert L -- Montironi, Rodolfo -- Magi-Galluzzi, Cristina -- Kantoff, Philip W -- Balk, Steven P -- Liu, X Shirley -- Brown, Myles -- CA090381/CA/NCI NIH HHS/ -- CA097186/CA/NCI NIH HHS/ -- CA111803/CA/NCI NIH HHS/ -- CA131945/CA/NCI NIH HHS/ -- CA166507/CA/NCI NIH HHS/ -- CA85859/CA/NCI NIH HHS/ -- CA89021/CA/NCI NIH HHS/ -- CA90381/CA/NCI NIH HHS/ -- GM99409/GM/NIGMS NIH HHS/ -- K99 CA166507/CA/NCI NIH HHS/ -- P50 CA090381/CA/NCI NIH HHS/ -- R01 GM099409/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Dec 14;338(6113):1465-9. doi: 10.1126/science.1227604.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23239736" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Castration
;
Cell Line, Tumor
;
Cohort Studies
;
Gene Expression Regulation, Neoplastic
;
Gene Silencing
;
Humans
;
Jumonji Domain-Containing Histone Demethylases/metabolism
;
Male
;
Methyltransferases/chemistry/genetics/metabolism
;
Mice
;
Mice, Inbred ICR
;
Mice, SCID
;
Oncogene Proteins/genetics/*metabolism
;
Polycomb Repressive Complex 2/genetics/*metabolism
;
Prostatic Neoplasms/genetics/*metabolism/mortality
;
Protein Structure, Tertiary
;
Receptors, Androgen/metabolism
;
Xenograft Model Antitumor Assays
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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