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Association of gene expression with sequential proliferation, differentiation and tumour formation in murine skin

By Katie Ridd, Shu-Dong Zhang, Richard E. Edwards, Reginald Davies, Peter Greaves, Alison Wolfreys, Andrew G. Smith and Timothy W. Gant


The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access\ud version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.orgDifferential gene expression in two established initiation and promotion skin carcinogenesis models during promotion and tumour formation was determined by microarray technology with the purpose of distinguishing those genes more associated with neoplastic transformation from those linked with proliferation and differentiation. The first model utilised\ud dimethylbenz[a]anthracene initiation and 12-O-tetradecanoylphorbol 13-acetate (TPA) promotion in the FVB/N mouse, and the second TPA promotion of the Tg.Ac mouse, which is endogenously initiated by virtue of an activated Ha-ras transgene. Comparison of gene expression profiles\ud across the two models identified genes whose altered expression was associated with papilloma formation rather than TPA induced proliferation and differentiation. DMBA suppressed TPA induced differentiation which allowed identification of those genes associated more specifically with differentiation rather than proliferation. EASE (Expression Analysis Systemic Explorer)\ud indicated a correlation between muscle associated genes and skin differentiation while genes involved with protein biosynthesis were strongly correlated with proliferation. For verification the\ud altered expression of selected genes were confirmed by RT-PCR; Carbonic anhydrase 2,\ud Thioredoxin 1 and Glutathione S-transferase omega 1 associated with papilloma formation and Enolase 3, Cystatin β and Filaggrin associated with TPA induced proliferation and differentiation. \ud In situ analysis located the papillomas Glutathione S-transferase omega 1 expression to the proliferating areas of the papillomas. Thus we have identified profiles of differential gene expression associated with the tumourgenesis and promotion stages for skin carcinogenesis in\ud the mouse

Publisher: Oxford University Press
Year: 2006
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