Document Detail


Epigenetic reprogramming as a key contributor to melanocyte malignant transformation.
MedLine Citation:
PMID:  21343701     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Melanoma progression requires deregulation of gene expression by currently uncharacterized epigenetic mechanisms. A mouse model based on changes in cell microenvironment was developed by our group to study melanocyte malignant transformation. Melanoma cell lines (4C11- and 4C11+) were obtained as result of 5 sequential anchorage blockades of non-tumorigenic melan-a melanocytes. Melan-a cells submitted to 4 de-adhesion cycles were also established (4C), are non-tumorigenic and represent an intermediary phase of tumor progression. The aim of this work was to identify factors contributing to epigenetic modifications in early and later phases of malignant transformation induced by anchorage impediment. Epigenetic alterations occur early in tumorigenesis; 4C cell line shows changes in global and gene-specific DNA methylation and histone marks. Many histone modifications differ between melan-a, 4C, 4C11- (non-metastatic melanoma cell line) and 4C11+ (metastatic melanoma cell line) which could be associated with changes in gene and microRNA expression. These epigenetic alterations seem to play a key role in malignant transformation since melanocytes treated with 5-Aza-2'-deoxycytidine before each anchorage blockade do not transform. Some epigenetic changes seem to be also responsible for the maintenance of malignant phenotype, since melanoma cell lines (4C11- and 4C11+) treated in vitro with 5-Aza-2'-deoxycytidine or Trichostatin A showed reduction of tumor growth in vivo. Changes in gene expression reflecting cell adaptation to new environment were also observed. We propose a model in which sustained microenvironmental stress in melanocytes results in epigenetic reprogramming. Thus, after adaptation, cells may acquire epigenetic marks that could contribute to the establishment of a malignant phenotype.
Authors:
Fernanda Molognoni; Adriana T Cruz; Fabiana M Meliso; Alice S Morais; Camila F Souza; Patrícia Xander; Jared M Bischof; Fabrício F Costa; Marcelo B Soares; Gangning Liang; Peter A Jones; Miriam G Jasiulionis
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-04-01
Journal Detail:
Title:  Epigenetics : official journal of the DNA Methylation Society     Volume:  6     ISSN:  1559-2308     ISO Abbreviation:  Epigenetics     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-29     Completed Date:  2011-08-26     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  101265293     Medline TA:  Epigenetics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  450-64     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cell Transformation, Neoplastic / chemically induced,  genetics*
DNA Methylation*
Epigenesis, Genetic*
Gene Expression Regulation, Neoplastic
Histones / metabolism*
Melanocytes / physiology*
Mice
Grant Support
ID/Acronym/Agency:
R37 CA082422/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Histones
Comments/Corrections

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