Genetic background modulates gene expression profile induced by skin irradiation in ptch1 mice.
OBJECTIVE
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 Ptch1(neo67/+) 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
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 Ptch1(neo67/+) mice of the Car-R cross and modulation of only eight genes in irradiated Ptch1(neo67/+) 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.
Galvan
Antonella
A
Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Noci
Sara
S
Mancuso
Mariateresa
M
Pazzaglia
Simonetta
S
Saran
Anna
A
Dragani
Tommaso A
TA
D000818:Animals; D002280:Basal Cell Carcinoma / Q000235:genetics; D003433:Crosses, Genetic; D020869:Gene Expression Profiling / Q000379:methods*; D020022:Genetic Predisposition to Disease; D016678:Genome; D018095:Germ-Line Mutation; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D012333:RNA, Messenger / Q000235:genetics / Q000528:radiation effects; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000235:genetics; D014158:Transcription, Genetic
D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface