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

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

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.
LanguageEnglish
Pages1556-66
JournalCarcinogenesis
Volume27
Issue number8
DOIs
Publication statusPublished - 2006

Fingerprint

Tetradecanoylphorbol Acetate
Papilloma
Gene Expression
Skin
Carcinogenesis
Genes
Neoplasms
Glutathione Transferase
Transcriptome
Cystatins
9,10-Dimethyl-1,2-benzanthracene
Thioredoxins
Carbonic Anhydrases
Phosphopyruvate Hydratase
Protein Biosynthesis
Transgenes
Technology
Muscles
Polymerase Chain Reaction

Keywords

  • differential gene expression
  • microarray
  • skin carcinogenesis
  • murine model

Cite this

Ridd, Katie ; Zhang, Shu-Dong ; Edwards, Richard E ; Davies, Reginald ; Greaves, Peter ; Wolfreys, Alison ; Smith, Andrew G ; Gant, Timothy W. / Association of gene expression with sequential proliferation, differentiation and tumor formation in murine skin. In: Carcinogenesis. 2006 ; Vol. 27, No. 8. pp. 1556-66.
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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.",
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Ridd, K, Zhang, S-D, Edwards, RE, Davies, R, Greaves, P, Wolfreys, A, Smith, AG & Gant, TW 2006, 'Association of gene expression with sequential proliferation, differentiation and tumor formation in murine skin.', Carcinogenesis, vol. 27, no. 8, pp. 1556-66. https://doi.org/10.1093/carcin/bgl007

Association of gene expression with sequential proliferation, differentiation and tumor formation in murine skin. / Ridd, Katie; Zhang, Shu-Dong; Edwards, Richard E; Davies, Reginald; Greaves, Peter; Wolfreys, Alison; Smith, Andrew G; Gant, Timothy W.

In: Carcinogenesis, Vol. 27, No. 8, 2006, p. 1556-66.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association of gene expression with sequential proliferation, differentiation and tumor formation in murine skin.

AU - Ridd, Katie

AU - Zhang, Shu-Dong

AU - Edwards, Richard E

AU - Davies, Reginald

AU - Greaves, Peter

AU - Wolfreys, Alison

AU - Smith, Andrew G

AU - Gant, Timothy W

PY - 2006

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N2 - 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.

AB - 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.

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KW - microarray

KW - skin carcinogenesis

KW - murine model

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DO - 10.1093/carcin/bgl007

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JO - Carcinogenesis

T2 - Carcinogenesis

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SN - 0143-3334

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ER -