Reduced expression of IL-18 is a marker of ultraviolet radiation-induced melanomas
Hacker, Elke, Muller, H. Konrad, Whiteman, David C., Pavey, Sandra, Hayward, Nicholas K., & Walker, Graeme J. (2008) Reduced expression of IL-18 is a marker of ultraviolet radiation-induced melanomas. International Journal of Cancer, 123(1), pp. 227-231.
We previously showed that mice carrying an activated Cdk4 mutation together with melanocyte-specific mutant Hras (Cdk4R24C/R24C/TPras) develop melanoma spontaneously, but penetrance is increased and age of onset reduced after neonatal UVR exposure. UVR-treated mice were more likely to develop multiple primary lesions, and these melanomas more often expressed Trp53, and less often expressed c-Myc, than melanomas from non-irradiated mice (1). These data suggest differences in mechanisms of tumorigenesis between melanomas developing spontaneously, or as a result of UVR exposure. To further delineate these differences we compared global gene expression between spontaneous and UVR-induced melanomas from these mice using microarrays. We found 264 genes differentially expressed between these groups (ANOVA, p<0.05). Selected candidate genes were validated using qRT-PCR, which confirmed upregulation of Gpr155 and Bmp7, and downregulation of Plagl1, Akap12 and Il18 in UVR-induced mouse melanomas. In humans, epidemiological studies suggest there may be two predominant pathways to melanoma development. One characterized by chronic UVR exposure and which leads mainly to melanomas on sun-exposed sites; the other associated with low UVR exposure and leading predominantly to melanomas on less exposed body sites. We found by immunohistochemical analysis comparing a series of human melanomas from the head (a chronically sun-exposed site; N=82) with a set from the trunk (an intermittently exposed site; N=65), that the prevalence of IL-18 expression was significantly lower in melanomas on the head (16%) than truncal melanomas (34%, p=0.011). We conclude that loss of IL-18 is a marker of UVR-induced melanoma, both in animal models and humans.
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|Item Type:||Journal Article|
|Additional Information:||Running title: Decreased IL-18 in UVR-induced melanoma|
|Keywords:||Melanoma, Ultraviolet radiation, Divergent pathway, IL-18|
|Subjects:||Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > PUBLIC HEALTH AND HEALTH SERVICES (111700) > Public Health and Health Services not elsewhere classified (111799)|
|Divisions:||Current > QUT Faculties and Divisions > Faculty of Health|
Current > Schools > School of Public Health & Social Work
|Copyright Owner:||Copyright 2008 John Wiley & Sons, Inc.|
|Copyright Statement:||The definitive version is available at www3.interscience.wiley.com|
|Deposited On:||11 Jun 2009 12:40|
|Last Modified:||29 Feb 2012 23:59|
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