Oncogenic BRAF(V600E) Induces Clastogenesis and UVB Hypersensitivity

Dennis A Simpson; Nathalay Lemonie; David S Morgan; Shobhan Gaddameedhi; William K Kaufmann

doi:10.3390/cancers7020825

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Oncogenic BRAF(V600E) Induces Clastogenesis and UVB Hypersensitivity

Journal article

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Oncogenic BRAF(V600E) Induces Clastogenesis and UVB Hypersensitivity

Dennis A Simpson, Nathalay Lemonie, David S Morgan, Shobhan Gaddameedhi and William K Kaufmann

Cancers, Vol.7(2), pp.1072-1090

06/17/2015

DOI: https://doi.org/10.3390/cancers7020825

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https://hdl.handle.net/2376/114710

PMCID: PMC4491700

PMID: 26091525

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https://doi.org/10.3390/cancers7020825View

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Abstract

UVB

melanoma

melanocytes

BRAF(V600E)

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.

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Title: Oncogenic BRAF(V600E) Induces Clastogenesis and UVB Hypersensitivity
Creators: Dennis A Simpson - Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, CB7295, Chapel Hill, NC 27599, USA. dennis@email.unc.edu
Nathalay Lemonie - Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, CB7295, Chapel Hill, NC 27599, USA. nlemoine@live.unc.edu
David S Morgan - Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, CB7295, Chapel Hill, NC 27599, USA. dscardamone@gmail.com
Shobhan Gaddameedhi - Department of Experimental and Systems Pharmacology, College of Pharmacy, Washington State University, Spokane, WA 99210, USA. shobhan.gaddameedhi@wsu.edu
William K Kaufmann - Center for Environmental Health and Susceptibility, University of North Carolina at Chapel Hill, CB7295, Chapel Hill, NC 27599, USA. wkarlk@med.unc.edu
Publication Details: Cancers, Vol.7(2), pp.1072-1090
Academic Unit: UNKNOWN
Publisher: Switzerland
Grant note: P30 CA016086 / NCI NIH HHS P30 ES010126 / NIEHS NIH HHS R00 ES022640 / NIEHS NIH HHS P01 ES014635 / NIEHS NIH HHS
Identifiers: 99900547505501842
Language: English
Resource Type: Journal article