Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA106925 | ENA |
REPOSITORIES: ENA
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Project description:This study analyzes gene expression associated with papilloma development in Tg.AC v-Ha-ras transgenic mice and identifies novel genes and biological processes that may be critical to skin carcinogenesis in these mice. Epidermal abrasion was used to synchronously induce epidermal regeneration in FVB/N wild type and transgenic Tg.AC mice. Skin papillomagenesis was uniquely induced in Tg.AC mice, and gene expression profiling was carried out using a 22,000 element mouse DNA microarray. Histological analysis showed that papillomas developed at a high rate by day 30 after abrasion in transgenic animals, while no papilloma developed in wild type mice. Transgene specific differentially expressed genes were identified at day 30 post-abrasion and these genes were annotated using EASE software and literature mining. Annotated and non-annotated genes associated with papilloma development were identified and clustering analysis revealed groups of genes that are coordinately expressed. A number of genes associated with differentiation and development were also physically clustered on mouse chromosome 16, including 16B3 that contains several Stefins and stefin-like genes, and 16A1 containing a number of keratin associated protein genes. Additional analyses presented here yield novel insights into the genes and processes involved in papilloma development in Tg.AC mice. Keywords: Time course of papilloma tumorigenesis between genetically modified strains after skin abrasion.
2008-04-11 | GSE11136 | GEO
Project description:This study analyzes gene expression associated with papilloma development in Tg.AC v-Ha-ras transgenic mice and identifies novel genes and biological processes that may be critical to skin carcinogenesis in these mice. Epidermal abrasion was used to synchronously induce epidermal regeneration in FVB/N wild type and transgenic Tg.AC mice. Skin papillomagenesis was uniquely induced in Tg.AC mice, and gene expression profiling was carried out using a 22,000 element mouse DNA microarray. Histological analysis showed that papillomas developed at a high rate by day 30 after abrasion in transgenic animals, while no papilloma developed in wild type mice. Transgene specific differentially expressed genes were identified at day 30 post-abrasion and these genes were annotated using EASE software and literature mining. Annotated and non-annotated genes associated with papilloma development were identified and clustering analysis revealed groups of genes that are coordinately expressed. A number of genes associated with differentiation and development were also physically clustered on mouse chromosome 16, including 16B3 that contains several Stefins and stefin-like genes, and 16A1 containing a number of keratin associated protein genes. Additional analyses presented here yield novel insights into the genes and processes involved in papilloma development in Tg.AC mice. Experiment Overall Design: Strains: Tg.AC vs FVB/N; Treatment: epidermal abrasion vs sham treatment, samples collected 3, 5, 9, 18, and 30 days post treatment; Microarray: 2-channel, pooled total RNA from 5 animals, 2 technical replicate arrays with dye-swaps.
2008-06-11 | E-GEOD-11136 | biostudies-arrayexpress
Project description:We have shown that activin promoted skin tumorigenesis in mice induced by the human papilloma virus 8 oncogenes. Activin attracted blood monocytes to the skin as revealed by depletion of CCR2-positive monocytes. To determine if activin also altered the gene expression profile of these cells, we performed RNA-Sequencing of macrophages FACS-sorted from the pre-cancerous ear skin. We have found that activin induces a pro-migratiory, pro-angiogenic and pro-tumorigenic genes in skin macrophages in vivo. This largely contributes to the pro-tumorigenic function of activin, since macrophage depletion delayed spontaneous tumorigenesis in HPV8-transgenic mice by reducing keratinocyte proliferation and angiogenesis.
2017-02-08 | GSE79086 | GEO
Project description:Expression and function of the oncogenic transcription factor AP-1 (mainly composed of Jun and Fos proteins) is required for neoplastic transformation of mouse and human keratinocytes in vitro and tumor promotion as well as malignant progression in vivo. Here, we describe the identification of novel Fos target genes using global gene expression profiling with samples from a tumor model of mouse skin (K5-SOS-F). We could identify 366 differentially expressed genes comparing expression profiles from tumor samples of control animals with samples derived form mice with a specific deletion of fos in keratinocytes. Keywords: Fos-deletion, Fos-floxed, K5-SOS-F mouse tumor model, skin papilloma, global gene expression, microarray, Fos target in skin carcinogenesis
2008-09-01 | GSE10218 | GEO
Project description:Background; The in vivo properties of HR-HPV E6 and E7 oncoproteins have been previously evaluated through the generation and characterization of HPV transgenic mouse strains. Although K14E6 transgenic mice develop spontaneous tumors of the skin epithelium, no spontaneous reproductive tract malignancies arise, unless the transgenic mice were treated chronically with 17β-estradiol. Taken together, these findings suggest that E6 performs critical functions in normal adult cervix and skin, highlighting the need to define E6-controlled transcriptional programs in these tissues. We evaluated the different expression profile of 14,000 genes in skin or cervix from young K14E6 transgenic mice compared with corresponding tissues from non-transgenic (FVB) mice. Result; Microarray analysis identified a total of 676 and 1154 genes that were significantly up and down-regulated, respectively, in skin from K14E6 transgenic mice. On the other hand, in cervix from K14E6 transgenic mice we found that only 97 and 252 genes were significantly up and down-regulated, respectively. One of the most affected processes in the skin from K14E6 transgenic mice was the cell cycle. We also found that skin from transgenic mice showed down-regulation in pro-apoptotic genes expression, particularly in those related to the extrinsic apoptotic pathway. In contrast, we observed up-regulation of anti-apoptotic genes. Another pathway that was severely affected in skin was the immune response. In cervix from transgenic mice, we could not find affected any gene related to the cell cycle and apoptosis pathways. Interestingly, we observed alterations in the expression of immune response genes in cervix from K14E6 transgenic mice. Pathways such as angiogenesis, cell junction, cytoskeleton, keratinocyte differentiation and epidermis development, showed different gene expression in skin or cervix from K14E6 transgenic mice. Conclusion; Alterations in gene expression identified in the current study might partially explain why our K14E6 transgenic mice present a more aggressive phenotype in the skin than in the cervix. Expression of the HPV16 E6 oncoprotein alters expression of genes that fell into several functional groups providing insights into pathways by which E6 deregulate cell cycle progression, apoptosis and the host resistance to infection and immune function, providing new opportunities for early diagnostic markers and therapeutic drug targets. Experiment Overall Design: We compared the expression paterns in the skin and cervix of K14E6 transgenic mice against the same tissues from non-transgenic FVB mice. For each tissue, we pooled total RNA from three different 6 week virgin mice. Total RNA from the cervix and lower reproductive tract and dorsal skin were obtained from fresh frozen tissue using Trizol. Total RNA was processed an hybridized onto Affymetrix Mouse Genome 430A 2.0 Arrays. For each sample, a technical replica was included.
2008-10-25 | E-GEOD-10702 | biostudies-arrayexpress
Project description:Background The in vivo properties of HR-HPV E6 and E7 oncoproteins have been previously evaluated through the generation and characterization of HPV transgenic mouse strains. Although K14E6 transgenic mice develop spontaneous tumors of the skin epithelium, no spontaneous reproductive tract malignancies arise, unless the transgenic mice were treated chronically with 17β-estradiol. Taken together, these findings suggest that E6 performs critical functions in normal adult cervix and skin, highlighting the need to define E6-controlled transcriptional programs in these tissues. We evaluated the different expression profile of 14,000 genes in skin or cervix from young K14E6 transgenic mice compared with corresponding tissues from non-transgenic (FVB) mice. Result Microarray analysis identified a total of 676 and 1154 genes that were significantly up and down-regulated, respectively, in skin from K14E6 transgenic mice. On the other hand, in cervix from K14E6 transgenic mice we found that only 97 and 252 genes were significantly up and down-regulated, respectively. One of the most affected processes in the skin from K14E6 transgenic mice was the cell cycle. We also found that skin from transgenic mice showed down-regulation in pro-apoptotic genes expression, particularly in those related to the extrinsic apoptotic pathway. In contrast, we observed up-regulation of anti-apoptotic genes. Another pathway that was severely affected in skin was the immune response. In cervix from transgenic mice, we could not find affected any gene related to the cell cycle and apoptosis pathways. Interestingly, we observed alterations in the expression of immune response genes in cervix from K14E6 transgenic mice. Pathways such as angiogenesis, cell junction, cytoskeleton, keratinocyte differentiation and epidermis development, showed different gene expression in skin or cervix from K14E6 transgenic mice. Conclusion Alterations in gene expression identified in the current study might partially explain why our K14E6 transgenic mice present a more aggressive phenotype in the skin than in the cervix. Expression of the HPV16 E6 oncoprotein alters expression of genes that fell into several functional groups providing insights into pathways by which E6 deregulate cell cycle progression, apoptosis and the host resistance to infection and immune function, providing new opportunities for early diagnostic markers and therapeutic drug targets. Keywords: Human_papillomavirus, transgenic mice, expression profile
2008-09-01 | GSE10702 | GEO
Project description:Cancer progresses through distinct stages and mouse models recapitulating traits of this progression are frequently used to explore genetic, morphological and pharmacological aspects of tumor development. To complement genomic investigations of this process, here we quantify phosphoproteomic changes in skin cancer development using the SILAC mouse technology coupled to high resolution mass spectrometry. We distill protein expression signatures from our data that distinguish between skin cancer stages. A distinct phosphoproteome of the two stages of cancer progression is identified which correlates with perturbed cell growth and implicates cell adhesion as a major driver of malignancy. Importantly, integrated analysis of phosphoproteomic data and prediction of kinase activity revealed PAK4-PKC/SRC network to be highly deregulated in SCC but not in papilloma. This detailed molecular picture, both at the proteome and phosphoproteome level, will prove useful for the study of mechanisms of tumor progression.
2013-03-13 | PXD000821 | Pride
Project description:Germline polymorphisms influence gene expression networks in normal mammalian tissues. Analysis of this genetic architecture can identify single genes and whole pathways that influence to complex traits including inflammation and cancer susceptibility. Changes in the genetic architecture during the development of benign and malignant tumours have not been investigated. Here, we document major changes in germline control of gene expression during skin tumour development as a consequence of cell selection, somatic genetic events, and changes in tumour microenvironment. Immune response genes such as Interleukin 18 and Granzyme E are under germline control in tumours but not in normal skin. Gene expression networks linked to tumour susceptibility and hair follicle stem cell markers in normal skin undergo significant reorganization during tumour progression. Our data highlight opposing roles of Interleukin-1 signaling networks in tumour susceptibility and tumour progression and have implications for the development of chemopreventive strategies to reduce cancer incidence. Skin tumors were induced on dorsal back skin from a Mus spretus / Mus musculus backcross ([SPRET/Ei X FVB/N] X FVB/N) mice by treatment of dorsal back skin with dimethyl benzanthracene (DMBA) and tetradecanoyl-phorbol acetate (TPA). This treatment induced multiple benign papillomas as well as malignant squamous cell carcinomas (SCC) and spindle cell carcinomas. Gene expression analysis was performed on mRNA extracted from 68 papillomas: two papillomas from each of 31 FVBBX mice and a single papilloma from six additional FVBBX mice. Papillomas were harvested when mice were sacrificed due to presence of a carcinoma or termination of the experiment.
2010-12-22 | E-GEOD-21263 | biostudies-arrayexpress
Project description:HPV16 E7 oncoprotein expression in K14E7 transgenic mice induces cervical cancer after 6 months of treatment with the co-carcinogen 17M-NM-2-estradiol. In untreated mice, E7 also induces skin tumors late in life, albeit at low penetrance. These findings indicate that E7 alters cellular functions in cervix and skin so as to predispose these organs to tumorigenesis. Using microarrays, we determined the global genes expression profile in cervical and skin tissue of young adult K14E7 transgenic mice without estrogen treatment. In these tissues, the E7 oncoprotein altered the transcriptional pattern of genes involved in several biological processes, including immune response, intracellular signaling cascades, cell adhesion, cell migration, development, cell cycle, growth, response to wounding and regulation of apoptosis. Among the E7-dysregulated genes were ones not previously known to be involved in cervical neoplasia, including DMBT1, GLI1 and 17M-NM-2HSD2 in cervix and MMP2, 12, 14, 19 and 27 in skin. The experiment consists of a total of 24 samples to evaluate the mRNA expression profiles in 4 different groups: skin biopsy of transgenic mice K14E7, cervix biopsy of transgenic mice K14E7, skin biopsy of FVB/N control virgin mice and cervix biopsy of FVB/N control virgin mice. Each group has 6 samples that had been processed in 3 pools of two samples (biological replicates) for a total of 6 samples for each condition.
2012-06-09 | E-GEOD-36219 | biostudies-arrayexpress
Project description:Purpose: The goals of this study are to compare NGS-derived skin transcriptome profiling (RNA-seq) in wild type mice with TTP delta ARE knock-in mutants. Methods: Skin mRNA profiles of approximately 27 week old wild-type (WT) and TTP delta ARE knock-in mice were generated by deep sequencing, with five biological replicates, using Illumina sequencers. The skin RNA samples were prepared from skin biopsies from treated but not papillomatous skin from mice treated with a standard DMBA-TPA protocol for 20 weeks. The sequence reads that passed quality filters were mapped to mm10 with STAR Aligner followed by featureCounts and DESeq2 anlysis. Results: We observed 1144 statistically differentially expressed genes (232 and 912 up- and down-regulated genes in TTP delta ARE mice, respectively, with fold changes >2 and FDR<0.05. Conclusions: Regulated overexpression of TTP by a stablizing deletion in the 3'UTR of its mRNA causes many changes in gene expression in mice subjected to a standard skin papilloma protocol.
2021-04-13 | GSE148199 | GEO