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Genetic variation in IRF4 expression modulates growth characteristics, tyrosinase expression and interferon-gamma response in melanocytic cells.
- Source :
-
Pigment cell & melanoma research [Pigment Cell Melanoma Res] 2018 Jan; Vol. 31 (1), pp. 51-63. Date of Electronic Publication: 2017 Oct 23. - Publication Year :
- 2018
-
Abstract
- 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.<br /> (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Subjects :
- Antiviral Agents pharmacology
Cell Proliferation
Cell Survival
Cells, Cultured
Gene Expression Regulation
Genetic Predisposition to Disease
Genotype
Humans
Melanocytes drug effects
Melanocytes metabolism
Melanoma drug therapy
Melanoma genetics
Melanoma metabolism
Ultraviolet Rays
Interferon Regulatory Factors genetics
Interferon Regulatory Factors metabolism
Interferon-gamma pharmacology
Melanocytes pathology
Melanoma pathology
Monophenol Monooxygenase metabolism
Polymorphism, Single Nucleotide
Subjects
Details
- Language :
- English
- ISSN :
- 1755-148X
- Volume :
- 31
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Pigment cell & melanoma research
- Publication Type :
- Academic Journal
- Accession number :
- 28755520
- Full Text :
- https://doi.org/10.1111/pcmr.12620