期刊
PIGMENT CELL & MELANOMA RESEARCH
卷 31, 期 1, 页码 51-63出版社
WILEY
DOI: 10.1111/pcmr.12620
关键词
interferon response; IRF4; melanocyte; melanoma; MITF; tyrosinase; UVR response
资金
- National Health and Medical Research Council [APP1043187, APP1083612, APP1099021]
- Cancer Council Queensland [APP1081219]
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 IFN gamma-mediated inflammatory response, is associated with melanomagenesis, we evaluated its effects in the context of IRF4 status. Manipulation of IRF4 levels followed by IFN gamma treatment revealed a subset of chemokines and immuno-evasive molecules that are sensitive to IRF4 expression level and genotype including CTLA4 and PD-L1.
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