Insulin-like Growth Factor-1 Impacts p53 Target Gene Induction in UVB-irradiated Keratinocytes and Human Skin
| Autor: | Mae Alexandra Carpenter, Rebekah J. Hutcherson, Amber J. Castellanos, Abdulrahman M.M. Alkawar, Michael G. Kemp, Mariyyah A.O. Madkhali, Ron Michael Johnson, Michael Bottomley |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Keratinocytes Ultraviolet Rays medicine.medical_treatment Human skin DNA polymerase eta Biochemistry Article 030207 dermatology & venereal diseases 03 medical and health sciences Insulin-like growth factor 0302 clinical medicine Transcription (biology) medicine Humans Physical and Theoretical Chemistry Insulin-Like Growth Factor I Cell Line Transformed Skin integumentary system Chemistry Growth factor DNA replication General Medicine Genes p53 In vitro 030104 developmental biology Gene Expression Regulation Cancer research Ex vivo Signal Transduction |
| Zdroj: | Photochem Photobiol |
| ISSN: | 1751-1097 |
| Popis: | The tumor suppressor protein p53 limits mutagenesis in response to ultraviolet-B (UVB) light exposure by activating the transcription of genes that mitigate the damaging effects of UVB radiation on DNA. Because most nonmelanoma skin cancers (NMSCs) occur in older individuals, it is important to understand the process of mutagenesis in the geriatric skin microenvironment. Based on previous studies demonstrating that geriatric skin expresses lower levels of the growth factor insulin-like growth factor-1 (IGF-1) than young adult skin, a role for IGF-1 in the regulation of p53 target genes was investigated in both human keratinocytes in vitro and human skin explants ex vivo. The products of the p53 target genes p21 and DNA polymerase eta (pol η) were found to be increased by UVB exposure in both experimental systems, and this induction was observed to be partially abrogated by depriving keratinocytes of IGF-1 in vitro or by the treatment of keratinocytes in vitro and human skin explants with an IGF-1 receptor antagonist. Because p21 and pol η function to limit mutagenic DNA replication following UVB exposure, these results suggest that NMSC risk in geriatric populations may be due to age-dependent decreases in IGF-1 signaling that disrupt p53 function in the skin. |
| Databáze: | OpenAIRE |
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