UV-induced DNA damage, repair, mutations and oncogenic pathways in skin cancer.
Repair of UV induced DNA damage is of key importance to UV-induced skin carcinogenesis. Specific signal transduction pathways that regulate cell cycling, differentiation and apoptosis are found to be corrupted in skin cancers, e.g., the epidermal growth-stimulating Hedgehog pathway in basal cell carcinomas (BCCs). Mutations in genes coding for proteins in these pathways lead to persistent disturbances that are passed along to daughter cells, e.g., mutations in the gene for the Patched (PTCH) protein in the Hedgehog pathway. Thus far only the point mutations in the P53 gene from squamous cell carcinomas and BCCs, and in PTCH gene from BCC of xeroderma pigmentosum (XP) patients appear to be unambiguously attributable to solar UV radiation. Solar UVB radiation is most effective in causing these point mutations. Other forms of UV-induced genetic changes (e.g., deletions) may, however, contribute to skin carcinogenesis with different wavelength dependencies.
de Gruijl
F R
FR
Department of Dermatology, Sylvius Lab, Leiden Univ. Med. Ctr., Wassenaarseweg 72, NL-2333 AL Leiden, The Netherlands. f.r.de_gruijl@lumc.nl
van Kranen
H J
HJ
Mullenders
L H
LH
D000818:Animals; D002280:Basal Cell Carcinoma / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair; D053823:Hedgehog Proteins; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D008934:Mitogens / Q000378:metabolism; D009154:Mutation; D009857:Oncogenes; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014466:Ultraviolet Rays / Q000009:adverse effects
D019941:Cyclin-Dependent Kinase Inhibitor p16; D053823:Hedgehog Proteins; D008934:Mitogens; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D020794:Receptor Protein-Tyrosine Kinases