Reference SummaryRidd K, Carcinogenesis 2006 Aug;27(8):1556-66

Title	Association of gene expression with sequential proliferation, differentiation and tumor formation in murine skin.
Authors	Ridd K; Zhang SD; Edwards RE; Davies R; Greaves P; Wolfreys A; Smith AG; Gant TW
Journal	Carcinogenesis
Volume	27
Issue	8
Year	2006
Pages	1556-66
Abstract	Differential gene expression in two established initiation and promotion skin carcinogenesis models during promotion and tumor formation was determined by microarray technology with the purpose of distinguishing the genes more associated with neoplastic transformation from those linked with proliferation and differentiation. The first model utilized 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, whereas 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 beta 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 tumorigenesis and promotion stages for skin carcinogenesis in the mouse.
Links	J:112054 – MGI References 16537558 – National Library of Medicine/PubMed

Models
Strain	Model Name	Treatment Agent(s)	Organ Affected	Frequency	Model Details
FVB/N	Skin - Dorsal region papilloma	12-O-tetradecanoylphorbol-13-acetate (TPA) dimethylbenzanthracene (DMBA)	Skin - Dorsal region	100
FVB/N	Skin - Dorsal region papilloma	12-O-tetradecanoylphorbol-13-acetate (TPA)	Skin - Dorsal region	0
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed	Skin - Dorsal region papilloma	12-O-tetradecanoylphorbol-13-acetate (TPA)	Skin - Dorsal region	100
FVB/NTac-Tg(Hba-x-v-Ha-ras)TG.ACLed	Skin - Dorsal region papilloma		Skin - Dorsal region	0