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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Ras and Rac1, Frequently Mutated in Melanomas, Are Activated by Superoxide Anion, Modulate Dnmt1 Level and Are Causally Related to Melanocyte Malignant Transformation

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Author(s):
Molognoni, Fernanda [1] ; Machado de Melo, Fabiana Henriques [1, 2] ; da Silva, Camila Tainah [1] ; Jasiulionis, Miriam Galvonas [1]
Total Authors: 4
Affiliation:
[1] Univ Fed Sao Paulo, Dept Farmacol, UNIFESP, Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, UNIFESP, Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: PLoS One; v. 8, n. 12 DEC 16 2013.
Web of Science Citations: 15
Abstract

A melanocyte malignant transformation model was developed in our laboratory, in which different melanoma cell lines were obtained after submitting the non-tumorigenic melanocyte lineage melan-a to sequential cycles of anchorage impediment. Our group has already showed that increased superoxide level leads to global DNA hypermemethylation as well increased Dnmt1 expression few hours after melanocyte anchorage blockade. Here, we showed that Ras/Rac1/ERK signaling pathway is activated in melanocytes submitted to anchorage impediment, regulating superoxide levels, global DNA methylation, and Dnmt1 expression. Interestingly, Ras and Rac1 activation is not related to codon mutations, but instead regulated by superoxide. Moreover, the malignant transformation was drastically compromised when melan-a melanocytes were submitted to sequential cycles of anchorage blockage in the presence of a superoxide scavenger. This aberrant signaling pathway associated with a sustained stressful condition, which might be similar to conditions such as UV radiation and inflammation, seems to be an early step in malignant transformation and to contribute to an epigenetic reprogramming and the melanoma development. (AU)

FAPESP's process: 11/09676-1 - DNMT1 gene transcriptional regulation by oxidative stress caused by anchorage blockade assays in melanocytes
Grantee:Camila Tainah da Silva
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 11/12306-1 - Epigenetic mechanisms as mediators of melanocyte malignant transformation associated with sustained stress condition
Grantee:Miriam Galvonas Jasiulionis
Support type: Regular Research Grants