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ABSTRACT:
PROVIDER: PRJNA141083 | ENA |
REPOSITORIES: ENA
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Project description:This SuperSeries is composed of the following subset Series: GSE29711: Molecular Mechanisms of Bortezomib Resistant Adenocarcinoma cells [CGH data] GSE29712: Molecular Mechanisms of Bortezomib Resistant Adenocarcinoma cells [GEP data] Refer to individual Series
2011-06-04 | E-GEOD-29713 | biostudies-arrayexpress
Project description:Molecular Mechanisms of Bortezomib Resistant Adenocarcinoma cells [CGH data]
| PRJNA153857 | ENA
Project description:Molecular Mechanisms of Bortezomib Resistant Adenocarcinoma cells [GEP data]
| PRJNA153859 | ENA
Project description:The model is based on publication:
Mathematical analysis of gefitinib resistance of lung adenocarcinoma caused by MET amplification
Abstract:
Gefitinib, one of the tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR), is effective for treating lung adenocarcinoma harboring EGFR mutation; but later, most cases acquire a resistance to gefitinib. One of the mechanisms conferring gefitinib resistance to lung adenocarcinoma is the amplification of the MET gene, which is observed in 5–22% of gefitinib-resistant tumors. A previous study suggested that MET amplification could cause gefitinib resistance by driving ErbB3-dependent activation of the PI3K pathway. In this study, we built a mathematical model of gefitinib resistance caused by MET amplification using lung adenocarcinoma HCC827-GR (gefitinib resistant) cells. The molecular reactions involved in gefitinib resistance consisted of dimerization and phosphorylation of three molecules, EGFR, ErbB3, and MET were described by a series of ordinary differential equations. To perform a computer simulation, we quantified each molecule on the cell surface using flow cytometry and estimated unknown parameters by dimensional analysis. Our simulation showed that the number of active ErbB3 molecules is around a hundred-fold smaller than that of active MET molecules. Limited contribution of ErbB3 in gefitinib resistance by MET amplification is also demonstrated using HCC827-GR cells in culture experiments. Our mathematical model provides a quantitative understanding of the molecular reactions underlying drug resistance.
2024-09-02 | BIOMD0000000827 | BioModels
Project description:Copy number and Gene expression profiling of HT-29 wild-type and bortezomib resistant cell lines Identification of mechanisms of bortezomib resistance
2011-06-04 | GSE29711 | GEO
Project description:Bortezomib (Velcade©) is widely used for the treatment of various human cancers, however, its mechanisms of action are not fully understood, particularly in myeloid malignancies. Bortezomib is a selective and reversible inhibitor of the proteasome. Paradoxically, we find that Bortezomib induces proteasome-independent degradation of TRAF6 protein, but not mRNA, in Myelodysplastic syndrome (MDS) and Acute Myeloid Leukemia (AML) cell lines and primary cells. The reduction in TRAF6 protein coincides with Bortezomib-induced autophagy, and subsequently with apoptosis in MDS/AML cells. RNAi-mediated knockdown of TRAF6 sensitized Bortezomib-sensitive and -resistant cell lines, underscoring the importance of TRAF6 in Bortezomib-induced cytotoxicity. Bortezomib-resistant cells expressing an shRNA targeting TRAF6 were resensitized to the cytotoxic effects of Bortezomib due to down-regulation of the proteasomal subunit alpha-1 (PSMA1). To uncover the molecular consequences following loss of TRAF6 in MDS/AML cells, we applied gene expression profiling and identified an apoptosis gene signature. Knockdown of TRAF6 in MDS/AML cell lines or patient samples resulted in rapid apoptosis and impaired malignant hematopoietic stem/progenitor function. In summary, we describe novel mechanisms by which TRAF6 is regulated through Bortezomib/autophagy-mediated degradation and by which it alters MDS/AML sensitivity to Bortezomib by controlling PSMA1 expression.
2012-06-15 | GSE38519 | GEO
Project description:Bortezomib (VelcadeM-BM-)) is widely used for the treatment of various human cancers, however, its mechanisms of action are not fully understood, particularly in myeloid malignancies. Bortezomib is a selective and reversible inhibitor of the proteasome. Paradoxically, we find that Bortezomib induces proteasome-independent degradation of TRAF6 protein, but not mRNA, in Myelodysplastic syndrome (MDS) and Acute Myeloid Leukemia (AML) cell lines and primary cells. The reduction in TRAF6 protein coincides with Bortezomib-induced autophagy, and subsequently with apoptosis in MDS/AML cells. RNAi-mediated knockdown of TRAF6 sensitized Bortezomib-sensitive and -resistant cell lines, underscoring the importance of TRAF6 in Bortezomib-induced cytotoxicity. Bortezomib-resistant cells expressing an shRNA targeting TRAF6 were resensitized to the cytotoxic effects of Bortezomib due to down-regulation of the proteasomal subunit alpha-1 (PSMA1). To uncover the molecular consequences following loss of TRAF6 in MDS/AML cells, we applied gene expression profiling and identified an apoptosis gene signature. Knockdown of TRAF6 in MDS/AML cell lines or patient samples resulted in rapid apoptosis and impaired malignant hematopoietic stem/progenitor function. In summary, we describe novel mechanisms by which TRAF6 is regulated through Bortezomib/autophagy-mediated degradation and by which it alters MDS/AML sensitivity to Bortezomib by controlling PSMA1 expression. TF-1 cells were transduced with lentivirus encoding shRNA targeting human TRAF6 and a negative control (pLKO) for 2.5 days. GFP positive cells were sorted for RNA exctration, labeling, and hybridization. A total of four samples were included, and two groups are assigned. Two replicates are for each group. Comparison comprises mRNA expression profile of TRAF6 knockdown (shT6) v.s. control vector (pLKO).
2012-06-14 | E-GEOD-38519 | biostudies-arrayexpress
Project description:Copy number and Gene expression profiling of HT-29 wild-type and bortezomib resistant cell lines Identification of mechanisms of bortezomib resistance
2011-06-04 | GSE29712 | GEO
Project description:MCL cells resistant to bortezomib show distinct tumor growth in vivo when compared to their bortezomib-sensitive counterpart We used microarrays to detail the factors underlying the increased tumorigenicity of bortezomib-resistant cells in vivo Global RNA expression in tumors harvested from SCID mice and derived from either bortezomib-sensitive or bortezomib-resistant MCL cell lines
2013-10-18 | E-GEOD-51371 | biostudies-arrayexpress
Project description:MCL cells resistant to bortezomib show distinct tumor growth in vivo when compared to their bortezomib-sensitive counterpart We used microarrays to detail the factors underlying the increased tumorigenicity of bortezomib-resistant cells in vivo
2013-10-18 | GSE51371 | GEO