Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Inflammation-Driven Carcinogenesis is Mediated through STING [skin]

ABSTRACT: Chronic stimulation of innate immune pathways by microbial agents or damaged tissue is known to promote inflammation-driven tumorigenesis by unclarified mechanisms1-3. Here we demonstrate that mutagenic 7,12-dimethylbenz(a)anthracene (DMBA), etoposide or cisplatin induces nuclear DNA leakage into the cytosol to intrinsically activate STING (Stimulator of Interferon Genes) dependent cytokine production. Inflammatory cytokine levels were subsequently augmented in a STING-dependent extrinsic manner by infiltrating phagocytes purging dying cells. Consequently, STING-/- mice, or wild type mice adoptively transferred with STING-/- bone marrow, were almost completely resistant to DMBA-induced skin carcinogenesis compared to their wild type counterparts. Our data emphasizes, for the first time, a role for STING in the induction of cancer, sheds significant insight into the causes of inflammation-driven carcinogenesis, and may provide therapeutic strategies to help prevent malignant disease Total RNA obtained from DMBA or acetone treated wild type (WT) or STING deficient (SKO) mouse skin or skin tumor was examined for gene expression.

ORGANISM(S): Mus musculus

SUBMITTER: BIJU ISSAC

PROVIDER: E-GEOD-57604 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Inflammation-Driven Carcinogenesis is Mediated through STING [MEFs]

Project description:Chronic stimulation of innate immune pathways by microbial agents or damaged tissue is known to promote inflammation-driven tumorigenesis by unclarified mechanisms1-3. Here we demonstrate that mutagenic 7,12-dimethylbenz(a)anthracene (DMBA), etoposide or cisplatin induces nuclear DNA leakage into the cytosol to intrinsically activate STING (Stimulator of Interferon Genes) dependent cytokine production. Inflammatory cytokine levels were subsequently augmented in a STING-dependent extrinsic manner by infiltrating phagocytes purging dying cells. Consequently, STING-/- mice, or wild type mice adoptively transferred with STING-/- bone marrow, were almost completely resistant to DMBA-induced skin carcinogenesis compared to their wild type counterparts. Our data emphasizes, for the first time, a role for STING in the induction of cancer, sheds significant insight into the causes of inflammation-driven carcinogenesis, and may provide therapeutic strategies to help prevent malignant disease Total RNA obtained from wild type murine embryonic fibroblasts (WT MEFs), STING deficient MEFs (SKO), Trex1 deficient MEFs (TKO), and both STING and Trex1 deficient MEFs (STKO) treated with DMBA and examined cytokine production by these cells.

2014-05-31 | E-GEOD-57603 | biostudies-arrayexpress

Single-cell RNA (10X Chromium) of mouse DMBA/TPA treated or control back skin and matched livers (2) (IKMB) 2022

Project description:We generated single cell transcriptomes from full thickness skin biopsies in mouse to quantify the skin cell types found in this species (control samples). To study how mouse skin changes upon exposure to a carcinogen, we performed a classical two-stage skin carcinogenesis experiment, wherein cancer is initiated by a single application of 7,12-dimethylbenz[a]-anthracene (DMBA) followed by repeated treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) to drive cell proliferation. After 10 weeks, full thickness skin biopsies were collected and used to generate single cell transcriptomes (treatment samples).

2023-11-21 | E-MTAB-12456 | biostudies-arrayexpress

Single-cell RNA (10X Chromium) of mouse DMBA/TPA treated or control back skin and matched livers (1) (DKFZ) 2022

2023-11-21 | E-MTAB-12454 | biostudies-arrayexpress

Network Analysis of Skin Tumor Progression Identifies a Rewired Genetic Architecture Affecting Inflammation and Tumor Susceptibility (papillomas)

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

Single-cell RNA (10X Chromium) of naked mole rate DMBA/TPA treated or control back skin and matched livers (CRUK B) 2022

Project description:We generated single cell transcriptomes from full thickness skin biopsies in naked mole-rat to quantify the skin cell types found in this species (control samples). To study if and how naked mole-rat skin changes upon exposure to a carcinogen, we performed a classical two-stage skin carcinogenesis experiment traditionally performed in mice, wherein cancer is initiated by a single application of 7,12-dimethylbenz[a]-anthracene (DMBA) followed by repeated treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) to drive cell proliferation. After 12 weeks, full thickness skin biopsies were collected and used to generate single cell transcriptomes (treatment samples).

2023-11-21 | E-MTAB-12461 | biostudies-arrayexpress

Single-cell RNA (10X Chromium) of naked mole rate DMBA/TPA treated or control back skin and matched livers (CRUK A) 2022

2023-11-21 | E-MTAB-12451 | biostudies-arrayexpress

Inflammation-Driven Carcinogenesis is Mediated through STING [skin]

2014-05-31 | GSE57604 | GEO

Inflammation-Driven Carcinogenesis is Mediated through STING [MEFs]

2014-05-31 | GSE57603 | GEO

Inflammation and tumor susceptibility in skin cancer

Project description:This SuperSeries is composed of the following subset Series: GSE12248: Genetic architecture of murine skin inflammation and tumor susceptibility GSE21247: Network Analysis of Skin Tumor Progression Identifies a Rewired Genetic Architecture Affecting Inflammation and Tumor Susceptibility (carcinomas) GSE21263: Network Analysis of Skin Tumor Progression Identifies a Rewired Genetic Architecture Affecting Inflammation and Tumor Susceptibility (papillomas) GSE26273: Network Analysis of Skin Tumor Progression Identifies a Rewired Genetic Architecture Affecting Inflammation and Tumor Susceptibility (aCGH) Refer to individual Series

2010-12-22 | E-GEOD-21264 | biostudies-arrayexpress

Inflammation-Driven Carcinogenesis is Mediated through STING

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-05-31 | E-GEOD-57605 | biostudies-arrayexpress