Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA262517 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The role of reproductive hormones in lung cancer is controversial; obervations from epidemiological studies support the possibilities that estrogen either promotes or protects against the disease. In an earlier study we reported that estradiol (E2) stimulated tumorigenesis in a genetically defined mouse model based on the conditional expression of oncogenic Kras and concomitant deletion of p53. The present study was meant to further examine the effects of estrogens in this model. Instead we found that tumorigenesis was inhibited by the presence of the ovaries and that E2 proved protective against tumorigenesis in ovariectomized animals. Specifically, E2 and the Esr1-specific agonist PPT reduced the number and size of tumors that developed; furthermore, the protective effects of these two steroids were dose-dependent. However, the Esr2 agonist DPN produced no effect. Since Esr2 predominates in the lung, these results suggest that the E2 effect is indirect, perhaps being mediated by an endocrine factor from another organ. Furthermore, the fact that the E2 effect in this second iteration of the mouse model was diametrically opposed to our earlier results suggests that genetic background plays a critical role in determining the effect of estrogen.
2015-09-25 | GSE61837 | GEO
Project description:Genetically engineered mouse models (GEMM) of cancer are powerful tools to study multiple aspects of caner biology. We developed a novel GEMM for lung squamous cell carcinoma (LSCC) by genetically combining overexpression of Sox2 with loss of Lkb1: Rosa26LSL-Sox2-IRES-GFP;Lkb1fl/fl (SL). We compared gene expression profiles of SL lung tumors with normal mouse lung tissue, mouse lung adenocarcinoma (LADC) tumors from KrasLSL-G12D/+;Trp53fl/fl (KP), mouse LSCC tumors from Lkb1fl/fl;Ptenfl/fl (LP) model as well as Lenti-Sox2-Cre Lkb1fl/fl.
2018-10-16 | GSE118246 | GEO
Project description:This microarray analysis was designed to determine (1) the impact of ERα expression on cellular TNFα response and estrogen-TNFα signaling crosstalk and (2) whether cigarette sidestream smoke particulates had estrogen-like action in human lung adenocarcinoma cells. The lung adenocarcinoma cell line CL1-5(TO-ERα)#18 was used as a model. Expression of ERα in this cell line is under Tet-on regulation and can be induced by addition of doxycycline. For the Objective 1, we found three types of TNFα responsive genes: estrogen/ERα-dependent, estrogen/ERα-enhanced, and estrogen/ERα-independent. For the Objective 2, the microarray data revealed that cigarette sidestream smoke particulates regulated given genes via ERα as 17β-estradiol in lung adenocarcinoma cells. Some of these ERα target genes had been identified previously.
2020-10-07 | GSE67475 | GEO
Project description:The mutational landscape of EGFR-, MYC-, and Kras- driven genetically-engineered mouse models of lung adenocarcinoma
| PRJNA339310 | ENA
Project description:As a master regulator of chromatin structure and function, the EZH2 lysine methyltransferase orchestrates transcriptional silencing of developmental gene networks. Overexpression of EZH2 is commonly observed in human epithelial cancers, such as non- small cell lung carcinoma (NSCLC), yet definitive demonstration of malignant transformation by deregulated EZH2 has proven elusive. Here, we demonstrate the causal role of EZH2 overexpression in NSCLC with a new genetically-engineered mouse model of lung adenocarcinoma. Deregulated EZH2 silences normal developmental pathways leading to epigenetic transformation independent from canonical growth factor pathway activation. As such, tumors feature a transcriptional program distinct from KRAS- and EGFR-mutant mouse lung cancers, but shared with human lung adenocarcinomas exhibiting high EZH2 expression. To target EZH2-dependent cancers, we developed a novel and potent EZH2 inhibitor that arises from a facile synthesis and possesses improved pharmacologic properties. JQEZ5 promoted the regression of EZH2-driven tumors in vivo, confirming oncogenic addiction to EZH2 in established tumors and providing the rationale for epigenetic therapy in a defined subset of lung cancer. Gene expression analysis of 7 samples, 3 EZH2 OE tumors, 2 EZH2 OE normal lung samples, and 2 WT lung samples
2015-11-01 | E-GEOD-70046 | biostudies-arrayexpress
Project description:As a master regulator of chromatin structure and function, the EZH2 lysine methyltransferase orchestrates transcriptional silencing of developmental gene networks. Overexpression of EZH2 is commonly observed in human epithelial cancers, such as non- small cell lung carcinoma (NSCLC), yet definitive demonstration of malignant transformation by deregulated EZH2 has proven elusive. Here, we demonstrate the causal role of EZH2 overexpression in NSCLC with a new genetically-engineered mouse model of lung adenocarcinoma. Deregulated EZH2 silences normal developmental pathways leading to epigenetic transformation independent from canonical growth factor pathway activation. As such, tumors feature a transcriptional program distinct from KRAS- and EGFR-mutant mouse lung cancers, but shared with human lung adenocarcinomas exhibiting high EZH2 expression. To target EZH2-dependent cancers, we developed a novel and potent EZH2 inhibitor that arises from a facile synthesis and possesses improved pharmacologic properties. JQEZ5 promoted the regression of EZH2-driven tumors in vivo, confirming oncogenic addiction to EZH2 in established tumors and providing the rationale for epigenetic therapy in a defined subset of lung cancer. ChIP-Seq for H3K27ac and H3K27me3 in murine normal and EZH2 overexpressed tumor lung tissue
2015-11-01 | E-GEOD-70045 | biostudies-arrayexpress
Project description:Background: LKB1 is among the most frequently altered tumor suppressors in lung adenocarcinoma. Despite being implicated in the regulation of a variety of cellular processes, the mechanisms by which LKB1 constrains lung tumor growth and progression remains an area of intense investigation. Purpose: To determine the extent of overlap in terms of the transcriptomic states arising from either Lkb1 deletion or Sik-targeting within cancer cells isolated from genetically engineered mouse models of oncogenic Kras-driven lung adenocarcinoma Approach: Cancer cells sorted from mouse lung tumors of defined genotypes were profiled by RNA-seq. Results: A strong overlap existed between Lkb1-deficient and Sik-targeted cancer cells both at the gene and pathways levels. Conclusions: Given the strong transcriptional overlap, loss of either Lkb1 or Sik appear to be functionally related.
2019-07-05 | GSE133895 | GEO
Project description:Rapid estrogen receptor signaling is essential for the protective effects of estrogen against vascular injury
| PRJNA152677 | ENA
Project description:RNA sequencing of genetically engineered mouse model lung tumors and normal mouse lung.
| PRJNA484951 | ENA
Project description:RNAseq of genetically engineered mouse model (GEMM) tumors
| PRJNA374857 | ENA