Melanoma Induction by Ultraviolet A but Not Ultraviolet B Radiation Requires Melanin Pigment

Overview

Journal Nat Commun

Specialty Biology

Date 2012 Jun 8

PMID 22673911

Citations 103

Authors

Frances P Noonan

M Raza Zaidi

Agnieszka Wolnicka-Glubisz

Miriam R Anver

Jesse Bahn

Albert Wielgus

Jean Cadet

Thierry Douki

Stephane Mouret

Margaret A Tucker

Anastas Popratiloff

Glenn Merlino

Edward C De Fabo

Affiliations

Soon will be listed here.

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.

Citing Articles

Transcriptional reprogramming triggered by neonatal UV radiation or Lkb1 loss prevents BRAF-induced growth arrest in melanocytes.

McGrail K, Granado-Martinez P, Orsenigo R, Caratu G, Nieto P, Heyn H Oncogene. 2025; .

PMID: 40057604 DOI: 10.1038/s41388-025-03339-7.

High-Glucose-Induced Metabolic and Redox Alterations Are Distinctly Modulated by Various Antidiabetic Agents and Interventions Against FABP5/7, MITF and ANGPTL4 in Melanoma A375 Cells.

Nishikiori N, Ohguro H, Watanabe M, Higashide M, Ogawa T, Furuhashi M Int J Mol Sci. 2025; 26(3).

PMID: 39940783 PMC: 11817646. DOI: 10.3390/ijms26031014.

Stochastic modeling of single-cell gene expression adaptation reveals non-genomic contribution to evolution of tumor subclones.

Hirsch M, Pal S, Rashidi Mehrabadi F, Malikic S, Gruen C, Sassano A Cell Syst. 2024; 16(1):101156.

PMID: 39701099 PMC: 11867576. DOI: 10.1016/j.cels.2024.11.013.

Current Insights into the Role of UV Radiation-Induced Oxidative Stress in Melanoma Pathogenesis.

Gieniusz E, Skrzydlewska E, Luczaj W Int J Mol Sci. 2024; 25(21).

PMID: 39519202 PMC: 11546485. DOI: 10.3390/ijms252111651.

Oxidative State in Cutaneous Melanoma Progression: A Question of Balance.

Benedusi M, Lee H, Lim Y, Valacchi G Antioxidants (Basel). 2024; 13(9).

PMID: 39334716 PMC: 11428248. DOI: 10.3390/antiox13091058.

References

Bachelor M, Bowden G . UVA-mediated activation of signaling pathways involved in skin tumor promotion and progression. Semin Cancer Biol. 2004; 14(2):131-8. DOI: 10.1016/j.semcancer.2003.09.017. View

Lookingbill D, Lookingbill G, Leppard B . Actinic damage and skin cancer in albinos in northern Tanzania: findings in 164 patients enrolled in an outreach skin care program. J Am Acad Dermatol. 1995; 32(4):653-8. DOI: 10.1016/0190-9622(95)90352-6. View

Diffey B, Healy E, Thody A, Rees J . Melanin, melanocytes, and melanoma. Lancet. 1995; 346(8991-8992):1713. DOI: 10.1016/s0140-6736(95)92882-0. View

Wei X, Walia V, Lin J, Teer J, Prickett T, Gartner J . Exome sequencing identifies GRIN2A as frequently mutated in melanoma. Nat Genet. 2011; 43(5):442-6. PMC: 3161250. DOI: 10.1038/ng.810. View

Damsky W, Curley D, Santhanakrishnan M, Rosenbaum L, Platt J, Gould Rothberg B . β-catenin signaling controls metastasis in Braf-activated Pten-deficient melanomas. Cancer Cell. 2011; 20(6):741-54. PMC: 3241928. DOI: 10.1016/j.ccr.2011.10.030. View

Mouret S, Baudouin C, Charveron M, Favier A, Cadet J, Douki T . Cyclobutane pyrimidine dimers are predominant DNA lesions in whole human skin exposed to UVA radiation. Proc Natl Acad Sci U S A. 2006; 103(37):13765-70. PMC: 1564232. DOI: 10.1073/pnas.0604213103. View

Ley R . Dose response for ultraviolet radiation A-induced focal melanocytic hyperplasia and nonmelanoma skin tumors in Monodelphis domestica. Photochem Photobiol. 2001; 73(1):20-3. DOI: 10.1562/0031-8655(2001)073<0020:drfura>2.0.co;2. View

Kunisada M, Sakumi K, Tominaga Y, Budiyanto A, Ueda M, Ichihashi M . 8-Oxoguanine formation induced by chronic UVB exposure makes Ogg1 knockout mice susceptible to skin carcinogenesis. Cancer Res. 2005; 65(14):6006-10. DOI: 10.1158/0008-5472.CAN-05-0724. View

Halaban R, Rubin J, Funasaka Y, Cobb M, Boulton T, Faletto D . Met and hepatocyte growth factor/scatter factor signal transduction in normal melanocytes and melanoma cells. Oncogene. 1992; 7(11):2195-206. View

10.

Recio J, Noonan F, Takayama H, Anver M, Duray P, Rush W . Ink4a/arf deficiency promotes ultraviolet radiation-induced melanomagenesis. Cancer Res. 2002; 62(22):6724-30. View

11.

Hocker T, Tsao H . Ultraviolet radiation and melanoma: a systematic review and analysis of reported sequence variants. Hum Mutat. 2007; 28(6):578-88. DOI: 10.1002/humu.20481. View

12.

Ravanat J, Douki T, Cadet J . Direct and indirect effects of UV radiation on DNA and its components. J Photochem Photobiol B. 2001; 63(1-3):88-102. DOI: 10.1016/s1011-1344(01)00206-8. View

13.

Tadokoro T, Yamaguchi Y, Batzer J, Coelho S, Zmudzka B, Miller S . Mechanisms of skin tanning in different racial/ethnic groups in response to ultraviolet radiation. J Invest Dermatol. 2005; 124(6):1326-32. DOI: 10.1111/j.0022-202X.2005.23760.x. View

14.

Meyskens Jr F, Farmer P, Yang S, Anton-Culver H . New perspectives on melanoma pathogenesis and chemoprevention. Recent Results Cancer Res. 2007; 174:191-5. DOI: 10.1007/978-3-540-37696-5_16. View

15.

Kvam E, Tyrrell R . The role of melanin in the induction of oxidative DNA base damage by ultraviolet A irradiation of DNA or melanoma cells. J Invest Dermatol. 1999; 113(2):209-13. DOI: 10.1046/j.1523-1747.1999.00653.x. View

16.

Ibrahim N, Haluska F . Molecular pathogenesis of cutaneous melanocytic neoplasms. Annu Rev Pathol. 2009; 4:551-79. DOI: 10.1146/annurev.pathol.3.121806.151541. View

17.

Takayama H, La Rochelle W, Anver M, Bockman D, Merlino G . Scatter factor/hepatocyte growth factor as a regulator of skeletal muscle and neural crest development. Proc Natl Acad Sci U S A. 1996; 93(12):5866-71. PMC: 39153. DOI: 10.1073/pnas.93.12.5866. View

18.

Viros A, Fridlyand J, Bauer J, Lasithiotakis K, Garbe C, Pinkel D . Improving melanoma classification by integrating genetic and morphologic features. PLoS Med. 2008; 5(6):e120. PMC: 2408611. DOI: 10.1371/journal.pmed.0050120. View

19.

De Fabo E, Noonan F, Fears T, Merlino G . Ultraviolet B but not ultraviolet A radiation initiates melanoma. Cancer Res. 2004; 64(18):6372-6. DOI: 10.1158/0008-5472.CAN-04-1454. View

20.

Pleasance E, Cheetham R, Stephens P, McBride D, Humphray S, Greenman C . A comprehensive catalogue of somatic mutations from a human cancer genome. Nature. 2009; 463(7278):191-6. PMC: 3145108. DOI: 10.1038/nature08658. View