| Epigenetic reprogramming as a key contributor to melanocyte malignant transformation. | |
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MedLine Citation:
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PMID: 21343701 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-04-01 |
Journal Detail:
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Title: Epigenetics : official journal of the DNA Methylation Society Volume: 6 ISSN: 1559-2308 ISO Abbreviation: Epigenetics Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-04-29 Completed Date: 2011-08-26 Revised Date: 2013-03-28 |
Medline Journal Info:
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Nlm Unique ID: 101265293 Medline TA: Epigenetics Country: United States |
Other Details:
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Languages: eng Pagination: 450-64 Citation Subset: IM |
Affiliation:
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Pharmacology Department, Universidade Federal de São Paulo, São Paulo, Brazil. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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R37 CA082422-14/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Histones |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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