Overexpression of D‐dopachrome tautomerase increases ultraviolet B irradiation‐induced skin tumorigenesis in mice
- 9 June 2021
- journal article
- research article
- Published by Wiley in The FASEB Journal
- Vol. 35 (7), e21671
- https://doi.org/10.1096/fj.202002631rrr
Abstract
Ultraviolet irradiation (UV) exposure is the leading factor underlying the development of skin malignancies. D-dopachrome tautomerase (D-DT), a functional homolog of macrophage migration inhibitory factor (MIF), has functional similarities to MIF. However, its role, unlike the role of MIF in photocarcinogenesis, is unknown. We therefore explored the role of D-DT in photocarcinogenesis by developing D-DT transgenic (D-DT Tg) mice and provided a research model for future studies targeting D-DT. Chronic UVB exposure accelerated tumor development in D-DT Tg mice compared with wild-type (WT) mice, with a higher incidence of tumors observed in D-DT Tg mice than in WT mice. In D-DT Tg irradiated mouse keratinocytes, the p53, PUMA, and Bax expression was lower than that in WT mice. These results indicate that D-DT Tg overexpression confers prevention against UVB-induced apoptosis in keratinocytes. Taken together, these findings support D-DT as a functionally important cytokine in photocarcinogenesis and potential therapeutic target for the prevention of photocarcinogenesis.Keywords
This publication has 41 references indexed in Scilit:
- The D -dopachrome tautomerase ( DDT ) gene product is a cytokine and functional homolog of macrophage migration inhibitory factor (MIF)Proceedings of the National Academy of Sciences of the United States of America, 2011
- The MIF Homologue D-Dopachrome Tautomerase Promotes COX-2 Expression through β-Catenin–Dependent and –Independent MechanismsMolecular Cancer Research, 2010
- Deficient deletion of apoptotic cells by macrophage migration inhibitory factor (MIF) overexpression accelerates photocarcinogenesisCarcinogenesis: Integrative Cancer Research, 2009
- Macrophage migration inhibitory factor (MIF) plays a critical role in pathogenesis of ultraviolet‐B (UVB) ‐induced nonmelanoma skin cancer (NMSC)The FASEB Journal, 2008
- Structural determinants of MIF functions in CXCR2-mediated inflammatory and atherogenic leukocyte recruitmentProceedings of the National Academy of Sciences of the United States of America, 2008
- Interleukin-1β and macrophage migration inhibitory factor (MIF) in dermal fibroblasts mediate UVA-induced matrix metalloproteinase-1 expressionJournal of Dermatological Science, 2008
- Ultraviolet B Radiation Upregulates the Production of Macrophage Migration Inhibitory Factor (MIF) in Human Epidermal KeratinocytesJournal of Investigative Dermatology, 1999
- Macrophage Migration Inhibitory Factor Is an Essential Immunoregulatory Cytokine in Atopic DermatitisBiochemical and Biophysical Research Communications, 1997
- Transcriptional activation of a hybrid promoter composed of cytomegalovirus enhancer and β-actin/β-globin gene in glomerular epithelial cells in vivoKidney International, 1997
- Identification of macrophage migration inhibitory factor (MIF) in human skin and its immunohistochemical localizationFEBS Letters, 1996