Document Detail


Metallothionein 1 h tumour suppressor activity in prostate cancer is mediated by euchromatin methyltransferase 1.
MedLine Citation:
PMID:  23355073     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Metallothioneins (MTs) are a group of metal binding proteins thought to play a role in the detoxification of heavy metals. Here we showed by microarray and validation analyses that MT1h, a member of MT, is down-regulated in many human malignancies. Low expression of MT1h was associated with poor clinical outcomes in both prostate and liver cancer. We found that the promoter region of MT1h was hypermethylated in cancer and that demethylation of the MT1h promoter reversed the suppression of MT1h expression. Forced expression of MT1h induced cell growth arrest, suppressed colony formation, retarded migration, and reduced invasion. SCID mice with tumour xenografts with inducible MT1h expression had lower tumour volumes as well as fewer metastases and deaths than uninduced controls. MT1h was found to interact with euchromatin histone methyltransferase 1 (EHMT1) and enhanced its methyltransferase activity on histone 3. Knocking down of EHMT1 or a mutation in MT1h that abrogates its interaction with EHMT1 abrogated MT1h tumour suppressor activity. This demonstrates tumour suppressor activity in a heavy metal binding protein that is dependent on activation of histone methylation.
Authors:
Yu-Chen Han; Zhong-Liang Zheng; Ze-Hua Zuo; Yan P Yu; Rui Chen; George C Tseng; Joel B Nelson; Jian-Hua Luo
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pathology     Volume:  230     ISSN:  1096-9896     ISO Abbreviation:  J. Pathol.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-14     Completed Date:  2013-07-16     Revised Date:  2014-07-06    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  England    
Other Details:
Languages:  eng     Pagination:  184-93     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / genetics,  metabolism*,  mortality,  secondary
Animals
Cell Line, Transformed
Cell Line, Tumor
Down-Regulation
Female
Gene Expression Regulation, Neoplastic
Histone-Lysine N-Methyltransferase / genetics,  metabolism*
Humans
Liver Neoplasms / genetics,  metabolism
Male
Metallothionein / genetics,  metabolism*
Mice
Mice, SCID
Microarray Analysis
Pennsylvania / epidemiology
Prostatic Neoplasms / genetics,  metabolism*,  mortality,  pathology
Survival Rate
Tumor Suppressor Proteins / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
R01 CA098249/CA/NCI NIH HHS; R01 CA098249/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Tumor Suppressor Proteins; 0/metallothionein 1 h, human; 9038-94-2/Metallothionein; EC 2.1.1.-/EHMT1 protein, human; EC 2.1.1.43/Histone-Lysine N-Methyltransferase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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