Melanoma induction by ultraviolet A but not ultraviolet B radiation requires melanin pigment

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Malignant melanoma of the skin (CMM) is associated with ultraviolet radiation exposure, but the mechanisms and even the wavelengths responsible are unclear. Here we use a mammalian model to investigate melanoma formed in response to precise spectrally defined ultraviolet wavelengths and biologically relevant doses. We show that melanoma induction by ultraviolet A (320–400 nm) requires the presence of melanin pigment and is associated with oxidative DNA damage within melanocytes. In contrast, ultraviolet B radiation (280–320 nm) initiates melanoma in a pigment-independent manner associated with direct ultraviolet B DNA damage. Thus, we identified two ultraviolet wavelength-dependent pathways for the induction of CMM and describe an unexpected and significant role for melanin within the melanocyte in melanomagenesis.

Abstract

Exposure to ultraviolet light is responsible for a large proportion of melanomas but the molecular mechanisms are unknown. In this study, melanoma is found to be induced in mice by UVA and UVB light in a pigment-dependent and -independent manner, respectively, resulting in different types of DNA damage.

Related collections

Most cited references 53

Record: found
Abstract: found
Article: not found

Exome sequencing identifies GRIN2A as frequently mutated in melanoma.

Xiaomu Wei, Vijay Walia, Jimmy Lin … (2011)

The incidence of melanoma is increasing more than any other cancer, and knowledge of its genetic alterations is limited. To systematically analyze such alterations, we performed whole-exome sequencing of 14 matched normal and metastatic tumor DNAs. Using stringent criteria, we identified 68 genes that appeared to be somatically mutated at elevated frequency, many of which are not known to be genetically altered in tumors. Most importantly, we discovered that TRRAP harbored a recurrent mutation that clustered in one position (p. Ser722Phe) in 6 out of 167 affected individuals (∼4%), as well as a previously unidentified gene, GRIN2A, which was mutated in 33% of melanoma samples. The nature, pattern and functional evaluation of the TRRAP recurrent mutation suggest that TRRAP functions as an oncogene. Our study provides, to our knowledge, the most comprehensive map of genetic alterations in melanoma to date and suggests that the glutamate signaling pathway is involved in this disease.

0 comments Cited 189 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: not found

Cyclobutane pyrimidine dimers are predominant DNA lesions in whole human skin exposed to UVA radiation.

S. Mouret, C. Baudouin, M Charveron … (2006)

Solar UV radiation is the most important environmental factor involved in the pathogenesis of skin cancers. The well known genotoxic properties of UVB radiation (290-320 nm) mostly involve bipyrimidine DNA photoproducts. In contrast, the contribution of more-abundant UVA radiation (320-400 nm) that are not directly absorbed by DNA remains poorly understood in skin. Using a highly accurate and quantitative assay based on HPLC coupled with tandem mass spectrometry, we determined the type and the yield of formation of DNA damage in whole human skin exposed to UVB or UVA. Cyclobutane pyrimidine dimers, a typical UVB-induced DNA damage, were found to be produced in significant yield also in whole human skin exposed to UVA through a mechanism different from that triggered by UVB. Moreover, the latter class of photoproducts is produced in a larger amount than 8-oxo-7,8-dihydro-2'-deoxyguanosine, the most common oxidatively generated lesion, in human skin. Strikingly, the rate of removal of UVA-generated cyclobutane pyrimidine dimers was lower than those produced by UVB irradiation of skin. Finally, we compared the formation yields of DNA damage in whole skin with those determined in primary cultures of keratinocytes isolated from the same donors. We thus showed that human skin efficiently protects against UVB-induced DNA lesions, whereas very weak protection is afforded against UVA. These observations emphasize the likely role played by the UVA-induced DNA damage in skin carcinogenesis and should have consequences for photoprotection strategies.

0 comments Cited 139 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: not found

β-catenin signaling controls metastasis in Braf-activated Pten-deficient melanomas.

William E. Damsky, David P. Curley, Manjula Santhanakrishnan … (2011)

Malignant melanoma is characterized by frequent metastasis, however, specific changes that regulate this process have not been clearly delineated. Although it is well known that Wnt signaling is frequently dysregulated in melanoma, the functional implications of this observation are unclear. By modulating β-catenin levels in a mouse model of melanoma that is based on melanocyte-specific Pten loss and Braf(V600E) mutation, we demonstrate that β-catenin is a central mediator of melanoma metastasis to the lymph nodes and lungs. In addition to altering metastasis, β-catenin levels control tumor differentiation and regulate both MAPK/Erk and PI3K/Akt signaling. Highly metastatic tumors with β-catenin stabilization are very similar to a subset of human melanomas. Together these findings establish Wnt signaling as a metastasis regulator in melanoma. Copyright © 2011 Elsevier Inc. All rights reserved.

0 comments Cited 135 times – based on 0 reviews      Review now

All references

Author and article information

Journal

Journal ID (nlm-ta): Nat Commun

Journal ID (iso-abbrev): Nat Commun

Title: Nature Communications

Publisher: Nature Pub. Group

ISSN (Electronic): 2041-1723

Publication date (Electronic): 06 June 2012

Volume: 3

Page: 884

Affiliations

[1 ]Laboratory of Photobiology and Photoimmunology, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University , Washington, District of Columbia 20037, USA.

[2 ]Laboratory of Cancer Biology and Genetics, National Cancer Institute, NIH , Bethesda, Maryland 20892, USA.

[3 ]Pathology/Histotechnology Laboratory, SAIC-Frederick, National Cancer Institute-Frederick , Frederick, Maryland 21702, USA.

[4 ]Laboratory of Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park , North Carolina 27709, USA.

[5 ]DSM/INAC/SCIB UMR-E 3 CEA/UJF FRE CNRS 3200/Laboratoire 'Lésions des Acides Nucléiques' , CEA-Grenoble 38054, France.

[6 ]Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH , Bethesda, Maryland 20892, USA.

[7 ]Center for Microscopy and Image Analysis, Office of the Vice-President, The George Washington University , Washington, District of Columbia 20037, USA.

[8 ]Present address: Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University , ul. Gronostajowa 7, Krakow 30-348, Poland (A.W.-G.).

[9 ]Present address: Duke Eye Center , 2351 Erwin Road, Durham, North Carolina 27705, USA (A.W.).

[10 ]Present address: Department of Toxicology and Chemical Risk, Army Institute for Biomedical Research , La Tronche 38700, France (S.M.).

Author notes

[a ] ecd@ 123456gwu.edu

Article

Publisher Item ID: ncomms1893

DOI: 10.1038/ncomms1893

PMC ID: 3621412

PubMed ID: 22673911

SO-VID: c6f06962-452c-45d6-b75a-9d985ff2d37f

License:

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

Melanoma induction by ultraviolet A but not ultraviolet B radiation requires melanin pigment

Read this article at

Abstract

Abstract

Related collections

Special Issue: Management of Viral Hepatitis in the Post-Omics Era

Most cited references 53

Exome sequencing identifies GRIN2A as frequently mutated in melanoma.

Cyclobutane pyrimidine dimers are predominant DNA lesions in whole human skin exposed to UVA radiation.

β-catenin signaling controls metastasis in Braf-activated Pten-deficient melanomas.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 6

Cited by 96

Most referenced authors 718