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

Antonella Galvan, Sara Noci, Mariateresa Mancuso, Simonetta Pazzaglia, Anna Saran, Tommaso A. Dragani

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1582-1586
Number of pages5
JournalInternational Journal of Radiation Oncology Biology Physics
Volume72
Issue number5
DOIs
Publication statusPublished - Dec 1 2008

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Keywords

  • Genetic susceptibility
  • Heredity
  • Mouse
  • Skin cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

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