Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA96817 | ENA |
REPOSITORIES: ENA
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Project description:The mouse agouti gene is normally expressed in the skin and regulates coat color pigmentation. Dominant regulatory mutations in the agouti gene, such as viable-yellow (Avy), cause ubiquitous over-expression of the wild-type gene product in every tissue in the body. As a result of this altered agouti expression, viable-yellow mice have solid yellow hair, they are obese and diabetic, and they have increased susceptibility to spontaneous and chemically induced tumors in a wide variety of tissues (e.g., skin, lung, liver, mammary gland and urinary bladder). Additionally, liver-specific expression of the agouti gene was shown to promote hepatocellular carcinogenesis, even in the absence of obesity and diabetes. Our lab recently extended these findings to show that the agouti gene also promotes skin cancer in the absence of obesity and diabetes. In K14-Agouti transgenic mice, the wild-type agouti gene is over-expressed in the skin under the regulatory control of the keratin 14 (K14) promoter. Over-expression of agouti in the skin results in yellow coat color without the obesity and diabetes. In two-stage skin carcinogenesis experiments the agouti protein was shown to act as a tumor promoter since it promotes the development of skin tumors in the K14-Agouti transgenic mice, but only after the skin was initiated with a single dose of 7, 12-dimethylbenz[a]anthrance (DMBA). These experiments set the stage for determining the mechanism of action of agouti protein in tumor promotion, which remains completely uncharacterized. As a first step in determining the role of agouti in skin cancer, we used cDNA microarray and quantitative real time polymerase chain reaction (QRT-PCR) analysis to identify and validate a set of differentially expressed genes in the skin of K14-Agouti transgenic mice at the promotion stage of carcinogenesis. Keywords: promotion stage of carcinogenesis, biological replicates,
2007-04-09 | GSE4641 | GEO
Project description:Transgenic mice expressing a truncated form of Zmiz1 in the skin develop spontaneous keratoacanthomas. In this experiment, a Cre-inducible transgene expressing a truncated form of Zmiz1 was introduced into mice. Activation of the transgene in these mice was achieved by breeding to K14-Cre transgenic animals. Double transgenic mice formed spontaenous keratoacanthomas with short latency.
2012-10-01 | GSE39360 | GEO
Project description:Transgenic mice expressing a truncated form of Zmiz1 in the skin develop spontaneous keratoacanthomas. In this experiment, a Cre-inducible transgene expressing a truncated form of Zmiz1 was introduced into mice. Activation of the transgene in these mice was achieved by breeding to K14-Cre transgenic animals. Double transgenic mice formed spontaenous keratoacanthomas with short latency. In this experiment, we generated gene expression profiles for five Zmiz1-induced keratoacanthomas and six normal skin samples.
2012-10-01 | E-GEOD-39360 | biostudies-arrayexpress
Project description:Infrequently (LRCs) and frequently (non-LRCs) dividing cells in the mouse epidermis are moleculary distinct. Fluorescence activated cell sorting (FACS) from back skin cells of quadruple-transgenic mice harboring K5-tTA, pTRE-H2B-GFP, K14-CreER and Rosa-tdTomato transgenes.
2016-09-01 | E-GEOD-70523 | biostudies-arrayexpress
Project description:Studies of osteopontin (OPN)-null mice have supported the role of OPN as a critical factor in the promotion of skin tumorigenesis. OPN is a highly inducible integrin- and CD44-interacting acidic glycoprotein with pleiotropic functions. In various types of cancer, elevated levels of OPN derived from cancer and from inflammatory cells are secreted into the microenvironment and the bloodstream. To determine whether OPN expressed by keratinocytes without any contribution from activated resident and infiltrating inflammatory cells promotes cutaneous tumor development, transgenic mice with constitutive epidermal expression of OPN in an OPN-null background, tg(K14-OPN) were generated. In photocarcinogenesis studies, tumor multiplicity and the incidence of cutaneous squamous cell carcinoma (cSCC) was similar between tg(K14-OPN) and wild-type (WT) mice. Consistent with our previous findings, constitutive epidermal expression of OPN enhanced the survival of acute ultraviolet B (UVB)-induced cell death compared with OPN-null mice and did not enhance UVB-induced epidermal hyperplasia compared to OPN-null or WT mice. Additionally, tg(K14-OPN) and OPN-null mice irradiated with long-term low dose UVB had significantly lower numbers of mutated p53 keratinocytes than WT mice. RNA-sequencing data from the epidermis of acute UVB-irradiated tg(K14-OPN) versus OPN-null mice compared to UVB-irradiated WT versus OPN-null mice suggests the importance of inflammation, Wnt, integrin and gonadotropin-releasing hormone receptor signaling in cutaneous tumorigenesis and implicates UVB irradiation and its induction of OPN in driving those pathways. In summary, the constitutive epidermal expression of OPN in OPN-null mice facilitates the development of cSCC comparable to WT mice.
2025-12-30 | GSE271536 | GEO
Project description:Full title: Cancer Associated Fibroblasts are activated in incipient neoplasia to orchestrate tumor promoting inflammation in an NF-κB-dependent manner. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and invasion. We demonstrate that CAFs also mediate tumor-enhancing inflammation. Using a mouse model of squamous skin cancer, we found a pro-inflammatory gene signature in CAFs isolated from dysplastic skin. This signature was also evident in CAFs from skin as well as mammary and pancreatic tumors in mice, and in human cancer. Surprisingly, the inflammatory signature was already activated in CAFs isolated from the incipient hyperplastic stage in multistep tumorigenesis. CAFs from this pathway functioned to promote macrophage recruitment, neovascularization and tumor growth in vivo, activities abolished when NF-κB signaling was inhibited. Additionally, we show that normal dermal fibroblasts can be âeducatedâ by carcinoma cells to express pro-inflammatory genes. Experiment Overall Design: We performed expression profiling analysis of dermal fibroblasts sorted from dysplastic skin tissue of K14-HPV16 mice, and from age matched non transgenic controls. This array analysis was repeated in triplicate. Amplified RNA was hybridized to the 430 2.0 Affymetrix mouse genome arrays.
2009-09-13 | E-GEOD-17817 | biostudies-arrayexpress
Project description:Bone morphogenetic protein (BMP) signalling plays a key role in the control of skin development and postnatal remodelling by regulating keratinocyte proliferation, differentiation and apoptosis. To study the role of BMPs in wound-induced epidermal repair, we used transgenic mice overexpressing the BMP downstream component Smad1 under the control of a K14 promoter as an in vivo model, as well as ex vivo and in vitro assays. K14-caSmad1 mice exhibited retarded wound healing associated with significant inhibition of proliferation and increased apoptosis in healing wound epithelium. Furthermore, microarray and qRT-PCR analyses revealed decreased expression of a number of cytoskeletal/cell motility-associated genes including wound-associated keratins (Krt16, Krt17) and Myo5a, in the epidermis of K14- caSmad1 mice versus wild-type controls during wound healing. BMP treatment significantly inhibited keratinocyte migration ex vivo, and primary keratinocytes of K14-caSmad1 mice showed retarded migration compared to wild-type controls. Finally, siRNA-mediated silencing of Bmpr-1B in primary mouse keratinocytes accelerated cell migration and was associated with increased expression of Krt16, Krt17 and Myo5a compared to controls. Thus, this study demonstrates that BMPs inhibit keratinocyte proliferation, cytoskeletal organization and migration in regenerating skin epithelium during wound healing, and raises a possibility for using BMP antagonists for the management of chronic wounds.
2013-11-01 | GSE50578 | GEO
Project description:Bone morphogenetic protein (BMP) signalling plays a key role in the control of skin development and postnatal remodelling by regulating keratinocyte proliferation, differentiation and apoptosis. To study the role of BMPs in wound-induced epidermal repair, we used transgenic mice overexpressing the BMP downstream component Smad1 under the control of a K14 promoter as an in vivo model, as well as ex vivo and in vitro assays. K14-caSmad1 mice exhibited retarded wound healing associated with significant inhibition of proliferation and increased apoptosis in healing wound epithelium. Furthermore, microarray and qRT-PCR analyses revealed decreased expression of a number of cytoskeletal/cell motility-associated genes including wound-associated keratins (Krt16, Krt17) and Myo5a, in the epidermis of K14- caSmad1 mice versus wild-type controls during wound healing. BMP treatment significantly inhibited keratinocyte migration ex vivo, and primary keratinocytes of K14-caSmad1 mice showed retarded migration compared to wild-type controls. Finally, siRNA-mediated silencing of Bmpr-1B in primary mouse keratinocytes accelerated cell migration and was associated with increased expression of Krt16, Krt17 and Myo5a compared to controls. Thus, this study demonstrates that BMPs inhibit keratinocyte proliferation, cytoskeletal organization and migration in regenerating skin epithelium during wound healing, and raises a possibility for using BMP antagonists for the management of chronic wounds. Two-condition experiment, Wild type vs. Smad1 overexpressing mice. Biological replicates: 2 replicates.
2013-11-01 | E-GEOD-50578 | biostudies-arrayexpress
Project description:Differentially expressed genes between WT and AtC3H17-overexpressing transgenic plants
| PRJNA305103 | ENA