posted on 2006-06-29, 12:40authored byKatie Ridd, Shu-Dong Zhang, Richard E. Edwards, Reginald Davies, Peter Greaves, Alison Wolfreys, Andrew G. Smith, Timothy W. Gant
Differential 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
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
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)
indicated a correlation between muscle associated genes and skin differentiation while genes involved with protein biosynthesis were strongly correlated with proliferation. For verification the
altered expression of selected genes were confirmed by RT-PCR; Carbonic anhydrase 2,
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.
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
the mouse.
History
Citation
Carcinogenesis, published as Advance Access, March 14, 2006
Published in
Carcinogenesis
Publisher
Oxford University Press
Available date
2006-06-29
Notes
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
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.org