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Cancers 2015, 7(2), 1072-1090; doi:10.3390/cancers7020825

Oncogenic BRAF(V600E) Induces Clastogenesis and UVB Hypersensitivity

1
Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, CB7295, Chapel Hill, NC 27599, USA
2
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, CB7295, Chapel Hill, NC 27599, USA
3
Department of Experimental and Systems Pharmacology, College of Pharmacy, Washington State University, Spokane, WA 99210, USA
4
Center for Environmental Health and Susceptibility, University of North Carolina at Chapel Hill, CB7295, Chapel Hill, NC 27599, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Chyi-Chia Richard Lee
Received: 24 April 2015 / Revised: 3 June 2015 / Accepted: 11 June 2015 / Published: 17 June 2015
(This article belongs to the Special Issue Current Topics in Cutaneous Melanoma)
View Full-Text   |   Download PDF [1148 KB, uploaded 17 June 2015]   |  

Abstract

The oncogenic BRAF(V600E) mutation is common in melanomas as well as moles. The roles that this mutation plays in the early events in the development of melanoma are poorly understood. This study demonstrates that expression of BRAF(V600E) is not only clastogenic, but synergizes for clastogenesis caused by exposure to ultraviolet radiation in the 300 to 320 nM (UVB) range. Expression of BRAF(V600E) was associated with induction of Chk1 pS280 and a reduction in chromatin remodeling factors BRG1 and BAF180. These alterations in the Chk1 signaling pathway and SWI/SNF chromatin remodeling pathway may contribute to the clastogenesis and UVB sensitivity. These results emphasize the importance of preventing sunburns in children with developing moles. View Full-Text
Keywords: BRAF(V600E); melanocytes; UVB; melanoma BRAF(V600E); melanocytes; UVB; melanoma
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Simpson, D.A.; Lemonie, N.; Morgan, D.S.; Gaddameedhi, S.; Kaufmann, W.K. Oncogenic BRAF(V600E) Induces Clastogenesis and UVB Hypersensitivity. Cancers 2015, 7, 1072-1090.

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