Similar Datasets
Project description:Expression data from MT-ret tumor tissue
| PRJNA592176 | ENA
Project description:Lymphatic endothelial cells (LEC) were isolated from MT-ret tumor tissue 12h after treatment with an Ang2-blocking antibody or control-IgG
2020-12-01 | GSE141262 | GEO
Project description:Genomic rearrangements leading to intragenic gene fusion are mainly found in some types of haematopoietic malignancies and sarcomas. Recently they have been described also in carcinomas such as the papillary thyroid histotype (60%-70%) and the Hürthle thyroid tumours (58%). The presence of junction oncogene constitutes an area of exciting research for emerging therapy as targeting the RET-PTC1 fusion oncogene by using small interfering RNA (siRNA) strategies since it is present only in the tumour cells and not in the surrounding normal cells. Therefore, we developed a siRNA against RET-PTC1 junction and assess its efficiency on the human papillary thyroid carcinoma cell line TPC-1 which spontaneously harbours the RET-PTC1 oncogene. The targeted genes are assessed by microarray analysis by comparing the regulated genes by the siRNA_RET-PTC1 vs a siRNA_RET developed on the RET part of the mRNA minus the siRNA_control that contain four mutation within the RET-PTC1 sequence. To test the targeted genes in the TPC-1 cell line that spontaneously harbours RET-PTC1 junction of two siRNAs developed: Within the RET-PTC1 junction, and in the mRNA RET part. A non-specific siRNA harbouring 4 mutations within the RET-PTC1 sequence was used as negative control (siRNA_control). By real-time PCR (Q-RT-PCR) we demonstrated that both siRNAs (siRNA_RET-PTC1 and siRNA_RET) significantly reduce RET mRNA levels of about 85 % in TPC-1 cells. The negative control did not show an effect of RET mRNA levels. Three independent transfections were performed on TPC-1 cells using 5 µl of Lipofectamine 2000 transfection reagent (Invitrogen, Cergy-Pontoise, France) and 50nM of i) siRNA_RET-PTC1 or ii) siRNA_RET or iii) siRNA_control that harbour 4 mutations within its sequence. Total RNAs of untreated cells and transfected cells were purified using the RNA cleanup and concentration kit (QIAGEN, Hilden, Germany) and gathered in 4 pools : 1) TPC-1 harbouring RET-PTC1 ; 2) TPC-1 silenced for RET-PTC1 with siRNA RET-PTC1 ; 3) TPC-1 silenced for siRNA RET ; 4) TPC-1 treated with the siRNA control.
2010-05-01 | E-TABM-746 | biostudies-arrayexpress
Project description:Increased treatment of metastatic castration resistant prostate cancer (mCRPC) with second-generation anti-androgen therapies (ADT) has coincided with a greater incidence of lethal, aggressive variant prostate cancer (AVPC) tumors that have lost androgen receptor (AR) signaling. AVPC tumors may also express neuroendocrine markers, termed neuroendocrine prostate cancer (NEPC). Recent evidence suggests kinase signaling may be an important driver of NEPC. To identify targetable kinases in NEPC, we performed global phosphoproteomics comparing AR-negative to AR-positive prostate cancer cell lines and identified multiple altered signaling pathways, including enrichment of RET kinase activity in the AR-negative cell lines. Clinical NEPC and NEPC patient derived xenografts displayed upregulated RET transcript and RET pathway activity. Pharmacologically inhibiting RET kinase in NEPC models dramatically reduced tumor growth and cell viability in mouse and human NEPC models. Our results suggest that targeting RET in NEPC tumors with high RET expression may be a novel treatment option.
2020-05-29 | PXD012970 | Pride
Project description:Increased treatment of metastatic castration resistant prostate cancer (mCRPC) with second-generation anti-androgen therapies (ADT) has coincided with a greater incidence of lethal, aggressive variant prostate cancer (AVPC) tumors that have lost androgen receptor (AR) signaling. AVPC tumors may also express neuroendocrine markers, termed neuroendocrine prostate cancer (NEPC). Recent evidence suggests kinase signaling may be an important driver of NEPC. To identify targetable kinases in NEPC, we performed global phosphoproteomics comparing AR-negative to AR-positive prostate cancer cell lines and identified multiple altered signaling pathways, including enrichment of RET kinase activity in the AR-negative cell lines. Clinical NEPC and NEPC patient derived xenografts displayed upregulated RET transcript and RET pathway activity. Pharmacologically inhibiting RET kinase in NEPC models dramatically reduced tumor growth and cell viability in mouse and human NEPC models. Our results suggest that targeting RET in NEPC tumors with high RET expression may be a novel treatment option.
2020-05-29 | PXD012971 | Pride
Project description:RET rearrangement is a newly identified oncogenic mutation in lung adenocarcinoma (LADC). Activity of dovitinib (TKI258), a potent inhibitor of FGFR, VEGFR, and PDGFR, in RET-rearranged LADC has not been reported. The aims of the study are to explore anti-tumor effects and mechanisms of acquired resistance of dovitinib in RET-rearranged LADC. Using structural modeling and in vitro analysis, we demonstrated that dovitinib induced cell cycle arrest at G0/G1 phase and apoptosis by selective inhibition of RET kinase activity and ERK1/2 signaling in RET-rearranged LC-2/ad cells. Strong anti-tumor effect of dovitinib was observed in LC-2/ad tumor xenograft model. To identify the acquired resistance mechanisms to dovitinib, LC-2/ad cells were exposed to increasing concentrations of dovitinib to generate LC-2/ad DR cells. Gene set enrichment analysis of gene expression and receptor tyrosine kinase assay revealed that Src, a central gene in focal adhesion , was activated in LC-2/ad DR cells. Saracatinib, a src kinase inhibitor, suppressed ERK1/2 phosphorylation and growth of LC-2/ad DR cells. Taken together, these findings suggest that dovitinib can be a potential therapeutic option for RET-rearranged LADC, in which acquired resistance to dovitinib can be overcome by targeting Src. To identify potential mechanisms of acquired resistance to dovitinib, we established LC-2/ad DR cells with acquired resistance to dovitinib by exposing LC-2/ad cells to increasing doses of dovitinib. LC-2/ad DR cells showed strong resistance to dovitinib (IC50> 3 μmol/L). Next, LC-2/ad and LC-2/ad DR cells were subjected to genome-wide gene expression profiling using cDNA microarray.
2015-09-01 | E-GEOD-69226 | biostudies-arrayexpress
Project description:RET rearrangement is a newly identified oncogenic mutation in lung adenocarcinoma (LADC). Activity of dovitinib (TKI258), a potent inhibitor of FGFR, VEGFR, and PDGFR, in RET-rearranged LADC has not been reported. The aims of the study are to explore anti-tumor effects and mechanisms of acquired resistance of dovitinib in RET-rearranged LADC. Using structural modeling and in vitro analysis, we demonstrated that dovitinib induced cell cycle arrest at G0/G1 phase and apoptosis by selective inhibition of RET kinase activity and ERK1/2 signaling in RET-rearranged LC-2/ad cells. Strong anti-tumor effect of dovitinib was observed in LC-2/ad tumor xenograft model. To identify the acquired resistance mechanisms to dovitinib, LC-2/ad cells were exposed to increasing concentrations of dovitinib to generate LC-2/ad DR cells. Gene set enrichment analysis of gene expression and receptor tyrosine kinase assay revealed that Src, a central gene in focal adhesion , was activated in LC-2/ad DR cells. Saracatinib, a src kinase inhibitor, suppressed ERK1/2 phosphorylation and growth of LC-2/ad DR cells. Taken together, these findings suggest that dovitinib can be a potential therapeutic option for RET-rearranged LADC, in which acquired resistance to dovitinib can be overcome by targeting Src.
2015-09-01 | GSE69226 | GEO
Project description:RET-aberrant cancer discovered as a relevant targetable oncogene in several types of tumors, whose inhibitors have marked efficacy. However, some of patients with RET-aberrant cancer are insensitive to RET- tyrosine kinase inhibitors (TKIs) and are clinically non-responders. Recently, drug-tolerant mechanisms have been gaining attention as targets for initial therapies aimed at overcoming drug resistance. However, the underlying mechanisms of drug-tolerant cells emergence treated with RET-TKIs derived from RET-aberrant cancer cells remains unknown. In this study, HER3 signal activity through YAP1 was led to maintaining cell survival and inducing the emergence of cells tolerant to RET-TKIs selpercatinib and pralsetinib in high YAP1 expressed RET- rearranged cancer cells. These results suggested that YAP1-HER3 axis plays pivotal roles for cell survival under an exposure with RET-TKIs in the intrinsic resistance to RET-TKIs and the emergence of tolerant cells by RET-TKIs in YAP1 expressed RET-aberrant cancer, suggesting that YAP1/HER3 inhibition and RET-TKIs is a highly potent combination for initial treatment.
2024-09-30 | GSE261830 | GEO
Project description:Blood (BEC) and lymphatic (LEC) endothelial cells were isolated from MT-ret tumors and 10x Genomics-based single-cell RNA-seq analysis was performed.
2020-12-01 | GSE141263 | GEO
Project description:Myeloproliferative neoplasms are frequently associated with aberrant constitutive tyrosine kinase (TK) activity resulting from point mutations or chimaeric fusion genes, such as BCR ABL1 or JAK2 V617F. We report here for the first time in hematological malignancies, two novel fusion genes involving the TK RET, BCR-RET and FGFR1OP-RET, in chronic myelo monocytic leukemia (CMML) cases. The two RET fusion genes lead to the aberrant activation of RET, are able to transform hematopoietic cells and skew the hematopoietic differentiation program towards the monocytic/macrophage lineage. We also report that the BCR-RET fusion protein is insensitive to Imatinib but sensitive to Sorafenib in vivo. CMML is an hematopoietic malignancy associated with the frequent activation of the RAS pathway. The RET fusion genes seems to constitutively mimic the same signaling pathway than RAS mutations. Overall, the RET fusion genes behaviors in the monocytic lineage underlie the role of the normal RET TK activity during the physiological monocytic differentiation. We analysed BAF/3 cells infected by BCR-RET, FGFR1OP-RET or BCR-ABL1P210 fusion genes retroviruses and sorted out using EGFP fluorescence, with Affymetrix GeneChip MouseGene 1.0 ST platform.
2012-01-06 | E-GEOD-34900 | biostudies-arrayexpress