Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse skin carcinogenesis in FVB/N and Tg.Ac mice

ABSTRACT: Female FVB/N and Tg.Ac (hemizygotes) mice 3-5 weeks of age were purchased from Harlan UK and Taconic UK, respectively. The mice were contained in an isolator and maintained at 19C with 50% relative humidity and a 12-hour light-dark cycle. Following a 1 week acclimatisation period the dorsal skin of the mice was shaved (approximately 8cm2 area) 2 days prior to commencing treatment. FVB/N mice (5 per group) were treated with dimethylbenz[a]anthracene (DMBA) (10ug/200ul in acetone) or vehicle control one week before promotion with TPA. TPA (2.5ug/200ul in acetone) was applied to the back of both FVB/N and Tg.Ac mice (5 per group) twice a week for up to 14 weeks; control mice received acetone. Mice were shaved and examined weekly for the presence of papillomas. At each time point (FVB/N mice 2, 4, 6 and 14 weeks of TPA promotion and Tg.Ac mice 4 days, 1, 2 and 9 weeks of TPA promotion) the mice were killed by cervical dislocation and the dorsal skin removed, a representative portion was fixed in 10% neutral buffered formalin and retained for histological analysis; the remainder was snap frozen in liquid nitrogen.

ORGANISM(S): Mus musculus

SUBMITTER: Katie Ridd

PROVIDER: E-MEXP-188 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Ridd Katie K Zhang Shu-Dong SD Edwards Richard E RE Davies Reginald R Greaves Peter P Wolfreys Alison A Smith Andrew G AG Gant Timothy W TW

Carcinogenesis 20060314 8

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 th ...[more]

PMID: 16537558

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Project description:Background: Germline polymorphisms can influence gene expression networks in normal mammalian tissues and can affect disease susceptibility. We and others have shown that analysis of this genetic architecture can identify single genes and whole pathways that influence complex traits including inflammation and cancer susceptibility. Whether germline variants affect gene expression in tumors which have undergone somatic alterations, and the extent to which these variants influence tumor progression, is unknown. Results: Using an integrated linkage and genomic analysis of a mouse model of skin cancer that produces both benign tumors and malignant carcinomas, we document major changes in germline control of gene expression during skin tumor development resulting from cell selection, somatic genetic events, and changes in the tumor microenvironment. The number of significant expression Quantitative Trait Loci (eQTLs) is progressively reduced in benign and malignant skin tumors when compared to normal skin. However, novel tumor-specific eQTLs are detected for several genes associated with tumor susceptibility, including Interleukin 18, Granzyme E, Sprouty homolog 2, and MAP kinase kinase 4. Conclusions: We conclude that the genetic architecture is substantially altered in tumors, and that eQTL analysis of tumors can identify host factors that influence the tumor microenvironment, MAP kinase signaling, and cancer susceptibility. A backcross was generated using male Mus spretus and female FVB/N mice; female F1 hybrids were mated with male FVB/N mice. Backcross mice (8-12 weeks old) received a single dose of DMBA (25 µg per mouse in 200 µl acetone). Starting one week after the initiation tumors were promoted with TPA (200 µl of 10-4 M solution in acetone) twice weekly for 20 weeks. Initiation and promotion were performed on doral back skin. DNA from 62 Carcinomas and matched untreated tails (used for normal DNA comparison) was obtained from tissue that was snap frozen when animals were sacrificed.

Dataset Information

Transcription profiling of mouse skin carcinogenesis in FVB/N and Tg.Ac mice

Publications

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

Similar Datasets

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