Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA97763 | ENA |
REPOSITORIES: ENA
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Project description:Adult T-cell leukemia (ATL) is a fatal neoplasia derived from HTLV-1 infected T lymphocytes exhibiting constitutive activation of NF-kB. To elucidate the complex molecular mechanism of anti-tumor effect of the proteasome inhibitor, bortezomib in ATL cells, we attempted to perform gene expression profiling. Experiment Overall Design: Four ATL cell lines were cultured with or without bortezomib, then analysed.
2008-06-14 | E-GEOD-6034 | biostudies-arrayexpress
Project description:Adult T-cell leukemia (ATL) is a fatal neoplasia derived from HTLV-1 infected T lymphocytes exhibiting constitutive activation of NF-kB. To elucidate the complex molecular mechanism of anti-tumor effect of the proteasome inhibitor, bortezomib in ATL cells, we attempted to perform gene expression profiling. Keywords: dose response
2007-10-09 | GSE6034 | GEO
Project description:BACKGROUND: The molecular mechanism of proteasome inhibitor-mediated anti-cancer activity has been logically hypothesized that the major pathway is inhibition of nuclear factor kappa-B (NF-kB) cascades, however, the precise mechanism is still unclear. Adult T-cell leukemia (ATL) is a fatal neoplasia derived from HTLV-1 infected T lymphocytes exhibiting constitutive activation of NF-kB. AIM: To elucidate the complex molecular mechanism of anti-tumor effect of the proteasome inhibitor, bortezomib in ATL cells, we attempted to perform network-based gene expression profiling. METHODS and RESULTS: Assessment of gene regulation by microarray analysis revealed that down-regulation of genes involved in anti-apoptosis (i.e., BCL2, and IAP5), up-regulation of genes related with apoptosis (i.e., FAF1), heat shock proteins (i.e., HSPA, HSPCA), and oxygen stress (i.e., heme oxygenase-1: HMOX-1). Gene network analysis employing the Bayesian statistical framework also suggests that HMOX-1 which is known as an inducer of reactive oxygen species (ROS), as well as SPARC play an important role in bortezomib-treated ATL cells. The HMOX-1 inhibitor, ZnPP, in addition to bortezomib partially inhibited the apoptotic effect of bortezomib on TaY cells. CONCLUSION: Our results suggest that in addition to the inhibition of NF-kB, bortezomib activated ROS pathway through HMOX-1, and SPARC may participate bortezomib-induced apoptosis, providing novel insight into the bortezomib mediated anti-tumor activity in ATL cells. Keywords: dose response and time course
2007-10-09 | GSE5794 | GEO
Project description:Molecular targets of bortezomib on adult T-cell leukemia cells
| PRJNA97157 | ENA
Project description:Tubulin binding small molecule PTC596 and proteasome inhibitor bortezomib cooperatively suppress the growth of myeloma cells
| PRJDB9313 | ENA
Project description:The proteasome is an appealing anti-cancer drug target and the proteasome inhibitor bortezomib has been approved for the treatment of certain types of malignancies. However, the molecular mechanisms underlying cancer cell resistance to bortezomib remain poorly understood. The pseudokinase TRIB3, an inhibitor of ATF4, is expressed at a high basal level in hepatoma cells and is strongly upregulated in response to bortezomib. To map genome-wide chromatin binding loci of TRIB3 protein, we fused a Flag tag to endogenous TRIB3 in HepG2 cells and performed ChIP-Seq. The results demonstrate that TRIB3 predominantly colocalizes with ATF4 on chromatin and the proteins reside in genomic regions containing the C/EBP-ATF motif. Bortezomib treatment leads to a robust enrichment of TRIB3 binding near genes induced by bortezomib and involved in the ER stress response and cell death. Disruption of TRIB3 increases C/EBP-ATF-driven transcription, augments ER stress and cell death in cells exposed to bortezomib, while TRIB3 overexpression enhances the cell survival. Thus, TRIB3, colocalizing with ATF4 and limiting its transcriptional activity, functions as a factor increasing resistance to bortezomib, while pharmacological over-activation of eIF2alpha-ATF4 can overcome the endogenous restraint mechanisms and sensitize cells to bortezomib.
2021-05-24 | GSE166958 | GEO
Project description:Molecular targets of HIV integrase inhibitor, MK-2048, on ATL cells
| PRJNA450607 | ENA
Project description:Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib
| PRJNA103715 | ENA
Project description:Purpose: We report the NGS-derived transcriptome profiling (paired-end RNA-seq) following proteasome inhibition in the multiple myeloma cell line MM.1S. Methods: MM.1S cells were treated for six hours with the synthetic proteasome inhibitor lactacystin or clinically-approved proteasome inhibitor bortezomib and RNA expression changes were quantified and compared to DMSO control-treated cells by RNA-sequencing.
2021-03-06 | GSE166122 | GEO
Project description:We previously showed that the proteasome inhibitor bortezomib (Velcade) induces cell death in a subset of human bladder cancer cell lines. Heat shock protein 72 kDa (Hsp72) is the major cytosolic stress-inducible molecular chaperone, and is thought to protect cells from proteasome inhibition. Here, using whole genome mRNA expression profiling, we identify isoform-specific expression of Hsp72 within a heterogeneous panel of bladder cancer cell lines. Bortezomib induced strong upregulation of both the HSPA1A and HSPA1B isoforms of Hsp72 in 253J B-V and SW780 (HSPA1A-high) cells, whereas only HSPA1B isoform expression was induced in UM-UC10 and UM-UC13 (HSPA1A-low) cells. Bortezomib stimulated the binding of heat shock factor-1 (HSF1) to the HSPA1A promoter much more efficiently in 253JB-V cells than in UM-UC13, but other HSF1 transcriptional targets were induced in all of the cell lines, implicating a specific defect in HSPA1A induction. Methylation-specific PCR revealed that the HSPA1A promoter was selectively methylated in the HSPA1A-low cell lines (UM-UC10 and UM-UC13), and exposure to the chromatin demethylating agent 5-aza-2'-deoxycytidine restored HSPA1A expression. Overexpression of Hsp72 promoted bortezomib resistance in the UM-UC10 and UM-UC13 cells, whereas transient knockdown of HSPA1B sensitized these cells to bortezomib. Exposure to the chemical HSF1 inhibitor KNK-437 promoted bortezomib sensitivity in the 253J B-V cells. Finally, shRNA-mediated stable knockdown of Hsp72 in 253J B-V promoted sensitivity to bortezomib both in vitro and in vivo. Together, our results suggest that a subset of human bladder cancer cells possess epigenetic modifications that shut off the HSPA1A promoter and increases dependency on the HSPA1B isoform to maintain Hsp72 expression. Our data also support the targeting of HSF1 or Hsp72 for use as tools to enhance bortezomib sensitivity in solid tumors.
2013-08-01 | GSE46132 | GEO