Project description:Platelet-derived growth factor receptor alpha (PDGFRα) expression is frequently observed in many kinds of cancer and is a candidate for therapeutic targeting. Here, we evaluated the biological significance of PDGFRα and PDGFRα blockade (using a fully humanized monoclonal antibody, 3G3) in uterine cancer. PDGFRα was expressed in uterine cancer cells, and its blockade with 3G3 resulted in inhibition of PDGFRα phosphorylation and of downstream signaling molecules, AKT and MAPK. Cell viability and invasive potential of uterine cancer cells were also inhibited by treatment of 3G3. Moreover, greater therapeutic effects were observed for 3G3 in combination with chemotherapy than for either drug alone in orthotopic mouse models of uterine cancer. These findings identify PDGFRα as an attractive therapeutic target for uterine cancer.
Project description:Platelet-derived growth factor receptor alpha (PDGFRα) expression is frequently observed in many kinds of cancer and is a candidate for therapeutic targeting. Here, we evaluated the biological significance of PDGFRα and PDGFRα blockade (using a fully humanized monoclonal antibody, 3G3) in uterine cancer. PDGFRα was expressed in uterine cancer cells, and its blockade with 3G3 resulted in inhibition of PDGFRα phosphorylation and of downstream signaling molecules, AKT and MAPK. Cell viability and invasive potential of uterine cancer cells were also inhibited by treatment of 3G3. Moreover, greater therapeutic effects were observed for 3G3 in combination with chemotherapy than for either drug alone in orthotopic mouse models of uterine cancer. These findings identify PDGFRα as an attractive therapeutic target for uterine cancer. Two groups of samples are included: 1.Hec-1A 2.Rl-95-2. Gene expression profiles of Hec-1A cells were compared to that of RL95-2 cells.
Project description:We conducted spatial transcriptomics data analysis of mouse tumors of gastric cancer treated with regorafenib, a multikinase inhibitor, which can suppress cancer-associated fibroblast growth by inhibiting platelet-derived growth factor receptor alpha and beta.
Project description:We profiled the transcriptome in two high-grade glioma (HGG) mouse models driven by mutated receptor tyrosine kinase (RTK) oncogenes, platelet-derived growth factor receptor alpha (PDGFRA), neurotrophic receptor tyrosine kinase 1 (NTRK1). In addition, transcriptome for normal mouse cortex was also profiled. The transcriptome was used to define transcription factor activity by integrating with whole proteome and phosphoproteome datasets.
Project description:The aim of this study was to investigate the inhibitory effect of TSU68, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor beta (PDGFRβ) and fibroblast growth factor receptor 1 (FGFR1), on colon cancer liver metastasis and to test the hypothesis that TSU68 modulates the microenvironment in the liver before the formation of metastasis.
Project description:Estrogen (E2) signaling through its nuclear receptor, estrogen receptor α (ERα) increases insulin-like growth factor 1 (IGF1) in the rodent uterus, which then initiates further signals via the IGF1 receptor (IGF1R). Directly administering IGF1 results in similar biological and transcriptional uterine responses. Our studies using global ERα-null mice demonstrated a loss of uterine biological responses of the uterus to E2 or IGF1 treatment, while maintaining transcriptional responses to IGF1. To address this discrepancy in the need for uterine ERα in mediating the IGF1 transcriptional vs. growth responses, we assessed the IGF1 transcriptional responses in PgrCre+Esr1f/f (called ERαUtcKO) mice, which selectively lack ERα in progesterone receptor (PGR) expressing cells, including all uterine cells, while maintaining ERα expression in other tissues and cells that do not express Pgr. Additionally, we profiled IGF1-induced ERα binding sites in uterine chromatin using ChIP-seq. Herein, we explore the transcriptional and molecular signaling that underlies our findings to refine our understanding of uterine IGF1 signaling and identify ERα-mediated and ERα-independent uterine transcriptional responses. Defining these mechanisms in vivo in whole tissue and animal contexts provides details of nuclear receptor mediated mechanisms that impact biological systems and have potential applicability to reproductive processes of humans, livestock and wildlife.
Project description:Estrogen (E2) signaling through its nuclear receptor, estrogen receptor α (ERα) increases insulin-like growth factor 1 (IGF1) in the rodent uterus, which then initiates further signals via the IGF1 receptor (IGF1R). Directly administering IGF1 results in similar biological and transcriptional uterine responses. Our studies using global ERα-null mice demonstrated a loss of uterine biological responses of the uterus to E2 or IGF1 treatment, while maintaining transcriptional responses to IGF1. To address this discrepancy in the need for uterine ERα in mediating the IGF1 transcriptional vs. growth responses, we assessed the IGF1 transcriptional responses in PgrCre+Esr1f/f (called ERαUtcKO) mice, which selectively lack ERα in progesterone receptor (PGR) expressing cells, including all uterine cells, while maintaining ERα expression in other tissues and cells that do not express Pgr. Additionally, we profiled IGF1-induced ERα binding sites in uterine chromatin using ChIP-seq. Herein, we explore the transcriptional and molecular signaling that underlies our findings to refine our understanding of uterine IGF1 signaling and identify ERα-mediated and ERα-independent uterine transcriptional responses. Defining these mechanisms in vivo in whole tissue and animal contexts provides details of nuclear receptor mediated mechanisms that impact biological systems and have potential applicability to reproductive processes of humans, livestock and wildlife.
Project description:The aims of the experiment were to profile the cardiac interstitial (non-myocyte) cell types in the adult mouse from injured and uninjured hearts and how they respond to modulation of platelet-derived growth factor receptor alpha (PDGFRa) signaling. Adult, male, C57BL/BJ mice were subject to either a myocardial infarction or sham injury, and given either PDGF-AB or PBS treatment via mini-pump, with single-cell RNA-seq profiles obtained from interstitial cells isolated from cardiac ventricles 3 or 7 days following surgery.
Project description:Three week old neurospheres cultured from 18, 20 and 22 week old human fetal brain tissue, generated from epidermal growth factor, platelet-derived growth factor, and platelet-derived growth factor and neurotrophin-3. Keywords: neurosphere development