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Genetic Background Modulates Gene Expression Profile Induced by Skin Irradiation in Ptch1 Mice

TitleGenetic Background Modulates Gene Expression Profile Induced by Skin Irradiation in Ptch1 Mice
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2008
AuthorsGalvan, A., Noci S., Mancuso Mariateresa, Pazzaglia Simonetta, Saran Anna, and Dragani T.A.
JournalInternational Journal of Radiation Oncology Biology Physics
KeywordsABS resins, Affymetrix, Animals, article, Basal Cell, basal cell carcinoma, Basal cell carcinomata, Basal cells, Bioactivity, carcinogenesis, Carcinoma, Cell Surface, Complex patterns, controlled study, Crosses, Extraction, Gene expression, Gene expression profiles, gene expression profiling, gene mutation, Genetic, Genetic backgrounds, genetic predisposition, Genetic Predisposition to Disease, Genetic resistances, genetic susceptibility, genetic transcription, Genome, Germ-Line Mutation, Heredity, irradiation, Knockout, Messenger, messenger RNA, Mice, microarray analysis, Modulation, mouse, Mouse genomes, Mutant Strains, mutation, nonhuman, Normal skins, Plants (botany), Polymerase Chain reactions, priority journal, progeny, protein Patched 1, radiation dose, Radiation exposure, radiosensitivity, real time polymerase chain reaction, Receptors, Reverse Transcriptase Polymerase Chain Reaction, reverse transcription polymerase chain reaction, RNA, Skin, skin cancer, skin carcinoma, Skin irradiations, Skin Neoplasms, Skin tumors, Time reverses, Transcriptase, Transcription, Transcriptional responses, Tumorigenesis, Tumors

Purpose: Ptch1 germ-line mutations in mice predispose to radiation-induced basal cell carcinoma of the skin, with tumor incidence modulated by the genetic background. Here, we examined the possible mechanisms underlying skin response to radiation in F1 progeny of Ptch1neo67/+ mice crossed with either skin tumor-susceptible (Car-S) or -resistant (Car-R) mice and X-irradiated (3 Gy) at 2 days of age or left untreated. Methods and Materials: We conducted a gene expression profile analysis in mRNA samples extracted from the skin of irradiated or control mice, using Affymetrix whole mouse genome expression array. Confirmation of the results was done using real-time reverse-transcriptase polymerase chain reaction. Results: Analysis of the gene expression profile of normal skin of F1 mice at 4 weeks of age revealed a similar basal profile in the nonirradiated mice, but alterations in levels of 71 transcripts in irradiated Ptch1neo67/+ mice of the Car-R cross and modulation of only eight genes in irradiated Ptch1neo67/+ mice of the Car-S cross. Conclusions: These results indicate that neonatal irradiation causes a persistent change in the gene expression profile of the skin. The tendency of mice genetically resistant to skin tumorigenesis to show a more complex pattern of transcriptional response to radiation than do genetically susceptible mice suggests a role for this response in genetic resistance to basal cell tumorigenesis. © 2008 Elsevier Inc. All rights reserved.


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Citation KeyGalvan20081582