Transcriptional changes in murine keratinocyte harbouring heterozygous or homozygous R245W p53 mutation in vitro
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ABSTRACT: Human epidermis is colonized by clones carrying UV light induced p53 mutations, thought to be the origin of keratinocyte derived cancers, but the cellular mechanisms underlying the formation of these clones are not well understood. To address this we generated a new conditional knock-in mouse model bearing one of the hot spot mutations, R245W (R248W in human), targeted to the p53 locus, with its expression linked to a GFP reporter to enable lineage tracing. This mutation is one of the most frequently observed in cutaneous squamous cell carcinomas. We find that when induced in individual epidermal interfollicular progenitor cells the p53 mutant cells are dominant over wild type keratinocytes expanding to colonize the majority of the interfollicular epidermis. This process is accelerated by sub erythema doses ultraviolet light exposure. In vitro analysis of the trancriptomes can explain the intrinsic function driving clonal expansion.
ORGANISM(S): Mus musculus
SUBMITTER: Tibor Nagy
PROVIDER: E-MTAB-4941 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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