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Aberrations of EZH2 in cancer

Aberrations of EZH2 in cancer
Aberrations of EZH2 in cancer
Control of gene expression is exerted at a number of different levels, one of which is the accessibility of genes and their controlling elements to the transcriptional machinery. Accessibility is dictated broadly by the degree of chromatin compaction, which is influenced in part by polycomb group proteins. EZH2, together with SUZ12 and EED, forms the polycomb repressive complex 2 (PRC2) which catalyses trimethylation of histone H3 lysine 27 (H3K27me3). PRC2 may recruit other polycomb complexes, DNA methyltransferases and histone deacetylases resulting in additional transcriptional repressive marks and chromatin compaction at key developmental loci. Overexpression of EZH2 is a marker of advanced and metastatic disease in many solid tumours including prostate and breast cancer. Mutation of EZH2 Y641 is described in lymphoma and results in enhanced activity whilst inactivating mutations are seen in poor prognosis myeloid neoplasms. No histone demethylating agents are currently available for treatment of patients but 3-deazaneplanocin (DZNep) reduces EZH2 levels and H3K27 trimethylation resulting in reduced cell proliferation in breast and prostate cancer cells in vitro. Furthermore, synergistic effects are seen for combined treatment with DNA demethylating agents and histone deacetylation inhibitors opening up the possibility of refined epigenetic treatments in the future.

1078-0432
2613-2618
Chase, Andrew
a40a09c2-3073-4655-ba0b-a802e34914b5
Cross, Nicholas C.
f87650da-b908-4a34-b31b-d62c5f186fe4
Chase, Andrew
a40a09c2-3073-4655-ba0b-a802e34914b5
Cross, Nicholas C.
f87650da-b908-4a34-b31b-d62c5f186fe4

Chase, Andrew and Cross, Nicholas C. (2011) Aberrations of EZH2 in cancer. Clinical Cancer Research, 17 (9), 2613-2618. (doi:10.1158/1078-0432.CCR-10-2156). (PMID:21367748)

Record type: Article

Abstract

Control of gene expression is exerted at a number of different levels, one of which is the accessibility of genes and their controlling elements to the transcriptional machinery. Accessibility is dictated broadly by the degree of chromatin compaction, which is influenced in part by polycomb group proteins. EZH2, together with SUZ12 and EED, forms the polycomb repressive complex 2 (PRC2) which catalyses trimethylation of histone H3 lysine 27 (H3K27me3). PRC2 may recruit other polycomb complexes, DNA methyltransferases and histone deacetylases resulting in additional transcriptional repressive marks and chromatin compaction at key developmental loci. Overexpression of EZH2 is a marker of advanced and metastatic disease in many solid tumours including prostate and breast cancer. Mutation of EZH2 Y641 is described in lymphoma and results in enhanced activity whilst inactivating mutations are seen in poor prognosis myeloid neoplasms. No histone demethylating agents are currently available for treatment of patients but 3-deazaneplanocin (DZNep) reduces EZH2 levels and H3K27 trimethylation resulting in reduced cell proliferation in breast and prostate cancer cells in vitro. Furthermore, synergistic effects are seen for combined treatment with DNA demethylating agents and histone deacetylation inhibitors opening up the possibility of refined epigenetic treatments in the future.

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More information

Accepted/In Press date: 2 March 2011
Published date: 1 May 2011

Identifiers

Local EPrints ID: 178049
URI: https://eprints.soton.ac.uk/id/eprint/178049
ISSN: 1078-0432
PURE UUID: 10132c70-b913-48b3-9683-827f44531242
ORCID for Nicholas C. Cross: ORCID iD orcid.org/0000-0001-5481-2555

Catalogue record

Date deposited: 22 Mar 2011 15:01
Last modified: 19 Nov 2019 01:50

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