Filters
Technology
Platform
Mus musculus
9 Downloadable Samples
Illumina HiSeq 2000
Description
KRAS mutations are the ost abundand driver mutations found in lung adenocarcinoma patients. Unfortunately, there are no clinical approved inhibitors available, to directly target mutant forms of KRAS. The aim of the study was to unravel the impact of upstream Egfr activation in signaling of mutated K-ras. We found that upregulation of G12D mutant Kras induced genes was significantly impaired when Egfr was knocked out. Our data suggests that signaling of mutant Kras depends on upstream activation. This finding may be exploited therapeutically by targeting EGFR in KRAS mutant patients. Overall design: We isolated mouse alveolar type II cells and induced the Kras G12D mutation, with and without concomitant Egfr knockout, in vitro. Cells lysates were analyzed 5 days following transgene induction.
Publication Title
JAK-STAT inhibition impairs K-RAS-driven lung adenocarcinoma progression.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples
SRP110058- Mus musculus
- 13 Downloadable Samples
- Illumina HiSeq 2000, Illumina HiSeq 2500
Description
First, transcriptome analysis of purified CD31+ endothelial cells (ECs) from VEGF-treated sprouting embryoid bodies showed angiogenesis as the top affected category when Apelin is not present. In addition, loss of Apelin resulted in the modulation of pathways in ECs related to vasculogenesis, cell adhesion and response to hypoxia. Ingenuity Pathway Analysis (IPA) further identified VEGFR pathway as the main upstream regulator affected in endothelial cells, closely followed by the TGFß1 and TNF pathways, all reduced in the absence of Apelin. The most inhibited genes from the VEGFR pathway in the absence of Apelin are angiogenesis-related genes. Second, transcriptome analysis of CD31+/CD105+ ECs sorted from Apelin wild-type and Apln-depleted tumors found a significant decrease in processes associated with endothelial cell proliferation and angiogenesis in ECs sorted out of Apelin-depleted tumors using IPA. Further, IPA predicted a decrease in the adhesion of granulocytes and upstream regulator analysis showed that proteins of the TGF-superfamily, Inhibin-ßA and TGF-ß1, as well as C/EBP-alpha, ß-Catenin, ErbB2 and EGFR are predicted to be inhibited upstream regulators in ECs isolated from Apelin-depleted tumors. Overall design: Transcriptome analysis of purified CD31+ endothelial cells from VEGF-treated in vitro sprouting vessels in Apelin presence or absence. Transcriptome analysis of tumor endothelial cells from Apelin wild-type and depleted conditions. We report the application of Smart-Seq2 sequencing to populations of 100 endothelial cells, sorted from tumors that were Apelin wild-type or depleted.
Publication Title
Apelin inhibition prevents resistance and metastasis associated with anti-angiogenic therapy.
Sample Metadata Fields
Sex, Specimen part, Cell line, Treatment, Subject
View Samples