title: Insulin-like growth factor-I and UVB photoprotection in human keratinocytes.
abstract: Ultraviolet radiation (UVR), in particular the UVB spectrum, is a risk factor for skin cancer development. The generation and accumulation of UVB-induced genetic mutations are fundamental premalignant events. Keratinocyte interactions between other cutaneous cell populations and the surrounding microenvironment determine cell fate and acute photoresponses. In this study, the importance of the insulin-like growth factor (IGF) system, in particular the insulin-like growth factor-I (IGF-I), on influencing key processes in the keratinocyte acute photoresponse was investigated. Exogenous IGF-I and other growth factors present in dermal fibroblast-conditioned media (CM) were found to significantly enhance keratinocyte survival following UVB irradiation in vitro. This pretreatment was also shown to cause a shift in the expression levels of various DNA damage response proteins. Consequently, this was associated with accelerated rates of UVB-induced cyclobutane pyrimidine dimer removal in these samples. Finally, activation of the IGF system influenced cell cycle progression in UVB-irradiated keratinocytes. Taken together, these results highlight the importance of the IGF signalling network in initiating the repair of potentially mutagenic DNA damage in human keratinocytes. The dysregulation of these processes may therefore have significant implications in the aetiology of skin cancers and other cutaneous diseases.
authors.affiliation: Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Qld, Australia.
authors.forename: Tara Lyn
authors.initials: TL
authors.lastname: Fernandez
authors.forename: Derek R
authors.initials: DR
authors.lastname: Van Lonkhuyzen
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Dawson
authors.forename: Michael G
authors.initials: MG
authors.lastname: Kimlin
authors.forename: Zee
authors.initials: Z
authors.lastname: Upton
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D000071877:Checkpoint Kinase 1; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005347:Fibroblasts; D006657:Histones / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects* / Q000528:radiation effects; D011494:Protein Kinases / Q000378:metabolism; D011740:Pyrimidine Dimers / Q000378:metabolism; D015398:Signal Transduction; D014466:Ultraviolet Rays
chemical_list: D017077:Culture Media, Conditioned; C468783:H2AX protein, human; D006657:Histones; D011740:Pyrimidine Dimers; D007334:Insulin-Like Growth Factor I; D011494:Protein Kinases; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D000071877:Checkpoint Kinase 1
keywords: UVB radiation; insulin-like growth factor; photocarcinogenesis; photoresponse