期刊
JOURNAL OF INVESTIGATIVE DERMATOLOGY
卷 137, 期 12, 页码 2613-2619出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jid.2017.05.037
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类别
资金
- American Institute for Cancer Research [10A103]
- joint UCB-CHORI
- [NIHR01 CA142879]
The effect of UVR on human basal cell carcinoma (BCC) epidemiology is complex-the incidence rises until approximately 30,000 hours of lifetime sunlight exposure and then plateaus. We hypothesize that UVR has opposing effects on BCC carcinogenesis-stimulatory via mutagenesis and inhibitory via production of hedgehog-inhibiting vitamin D-3 (D-3). We find that UVR exposure of ionizing radiation-treated Ptch1(+)/(-) mice accelerates BCC carcinogenesis in male mice, in which UVR does not produce D-3. By contrast, in female mice, in which UVR does produce D-3, UVR fails to accelerate BCC carcinogenesis, thus mirroring the plateauing in humans. However, if D-3 production is attenuated in female mice by deletion of keratinocyte lathosterol 5-desaturase, then UVR accelerates ionizing radiation-induced BCC carcinogenesis. Congruently, chronic topical application of D-3 inhibits ionizing radiation-induced BCC tumorigenesis. These findings confirm that UVR-induced production of D-3 in keratinocytes significantly restrains murine BCC tumorigenesis and demonstrate the counterintuitive conclusion that UVR has anti-BCC carcinogenic effects that can explain, at least in part, the complex relationship between exposure to UVR and BCC incidence.
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