Genetic variation in IRF4 expression modulates growth characteristics, tyrosinase expression and interferon-gamma response in melanocytic cells
| Autor: | Reuben S.Q. Kim, Stephen A. Ainger, Hilary X.L. Yong, Aaron G. Smith, Wen Lim, Melinda M. Ashcroft, Richard A. Sturm, Arish Soogrim, Dayana Nur Mahiuddin, Mitchell Fane, Graeme J. Walker, Scott A. Beatson, Darren J. Smit, Yash Chhabra, K. Jagirdar |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Chemokine Genotype Cell Survival Ultraviolet Rays Dermatology Antiviral Agents Polymorphism Single Nucleotide General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Interferon-gamma Interferon Melanoblast medicine Humans Interferon gamma Genetic Predisposition to Disease Viability assay Allele Melanoma Cells Cultured Cell Proliferation biology Monophenol Monooxygenase 030104 developmental biology Oncology Gene Expression Regulation Interferon Regulatory Factors Cancer research biology.protein Melanocytes medicine.drug IRF4 |
| Zdroj: | Pigment cellmelanoma research. 31(1) |
| ISSN: | 1755-148X |
| Popis: | A SNP within intron4 of the interferon regulatory factor4 (IRF4) gene, rs12203592*C/T, has been independently associated with pigmentation and age-specific effects on naevus count in European-derived populations. We have characterized the cis-regulatory activity of this intronic region and using human foreskin-derived melanoblast strains, we have explored the correlation between IRF4 rs12203592 homozygous C/C and T/T genotypes with TYR enzyme activity, supporting its association with pigmentation traits. Further, higher IRF4 protein levels directed by the rs12203592*C allele were associated with increased basal proliferation but decreased cell viability following UVR, an etiological factor in melanoma development. Since UVR, and accompanying IFNγ-mediated inflammatory response, is associated with melanomagenesis, we evaluated its effects in the context of IRF4 status. Manipulation of IRF4 levels followed by IFNγ treatment revealed a subset of chemokines and immuno-evasive molecules that are sensitive to IRF4 expression level and genotype including CTLA4 and PD-L1. |
| Databáze: | OpenAIRE |
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