Carcinogenesis Advance Access published online on March 14, 2006
Carcinogenesis, doi:10.1093/carcin/bgl007
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1 MRC Toxicology Unit, Hodgkin Building, Lancaster Road, PO BOX 138, University of Leicester, Leicester, LE1 9HN, UK
* To whom correspondence should be addressed. 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
Received July 25, 2005
Revised February 11, 2006
Accepted March 3, 2006
CANCER BIOLOGY
Association of gene expression with sequential proliferation, differentiation and tumour formation in murine skin
Katie Ridd 1,
Shu-Dong Zhang 1,
Richard E. Edwards,
Reginald Davies 1,
Peter Greaves 1,
Alison Wolfreys 2,
Andrew G. Smith 1,
and
Timothy W. Gant 1 *
2 Safety and Environmental Assurance Centre, Unilever, Colworth, Sharnbrook, Bedfordshire, MK44 1LQ, UK
Timothy W. Gant, E-mail: twg1{at}le.ac.uk
Abstract 
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.
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