This SuperSeries is composed of the SubSeries listed below.
Prospective identification of resistance mechanisms to HSP90 inhibition in KRAS mutant cancer cells.
Cell line
View SamplesInhibition of the HSP90 chaperone results in depletion of many signaling proteins that drive tumorigenesis, such as downstream effectors of KRAS, the most commonly mutated human oncogene. As a consequence, several small-molecule HSP90 inhibitors are being evaluated in clinical trials as anticancer agents. To prospectively identify mechanisms through which HSP90-dependent cancer cells evade pharmacologic HSP90 blockade, we generated multiple mutant KRAS-driven cancer cell lines with acquired resistance to the purine-scaffold HSP90 inhibitor PU-H71. All cell lines retained dependence on HSP90 function, as evidenced by sensitivity to short hairpin RNA-mediated suppression of HSP90AA1 or HSP90AB1 (also called HSP90 and HSP90, respectively), and exhibited two types of genomic alterations that interfere with the effects of PU-H71 on cell viability and proliferation: (i) a Y142N missense mutation in the ATP-binding domain of HSP90 that co-occurred with amplification of the HSP90AA1 locus, (ii) genomic amplification and overexpression of the ABCB1 gene encoding the MDR1 drug efflux pump. In support of a functional role for these alterations, exogenous expression of HSP90 Y142N conferred PU-H71 resistance to HSP90-dependent cells, and pharmacologic MDR1 inhibition with tariquidar or lowering ABCB1 expression restored sensitivity to PU-H71 in ABCB1-amplified cells. Finally, comparison with structurally distinct HSP90 inhibitors currently in clinical development revealed that PU-H71 resistance could be overcome, in part, by ganetespib (also known as STA9090) but not tanespimycin (also known as 17-AAG). Together, these data identify potential mechanisms of acquired resistance to small molecules targeting HSP90 that may warrant proactive screening for additional HSP90 inhibitors or rational combination therapies.
Prospective identification of resistance mechanisms to HSP90 inhibition in KRAS mutant cancer cells.
Cell line
View SamplesGene expression in NPM1 wildtype and mutated AML patients with high or low hsa_circ_0075001 expression
Circular RNAs of the nucleophosmin (NPM1) gene in acute myeloid leukemia.
Specimen part, Disease, Disease stage
View SamplesMicroarrays were used to detail the global programme of gene expression comparing wild-type and RNAi knock-down plants of SPT4-1 and SPT4-2
The transcript elongation factor SPT4/SPT5 is involved in auxin-related gene expression in Arabidopsis.
Age, Specimen part
View SamplesPanel of 53 melanoma cell lines were gene expression profiled by RNA-Seq for molecular classification Overall design: mRNA profiles of 53 melanoma cell lines
Interleukin 32 expression in human melanoma.
Disease, Disease stage, Cell line, Subject
View SamplesGene expression profile in circulating leukocytes identifies patients with coronary artery disease
Gene expression patterns in peripheral blood correlate with the extent of coronary artery disease.
Sex, Age, Specimen part, Race
View SamplesQuiescent and dividing hemopoietic stem cells (HSC) display marked differences in their ability to move between the peripheral circulation and the bone marrow. Specifically, long-term engraftment potential predominantly resides in the quiescent HSC subfraction, and G-CSF mobilization results in the preferential accumulation of quiescent HSC in the periphery. In contrast, stem cells from chronic myeloid leukemia (CML) patients display a constitutive presence in the circulation. To understand the molecular basis for this, we have used microarray technology to analyze the transcriptional differences between dividing and quiescent, normal, and CML-derived CD34+ cells.
Transcriptional analysis of quiescent and proliferating CD34+ human hemopoietic cells from normal and chronic myeloid leukemia sources.
Specimen part, Disease, Subject
View SamplesWe used microarrays to compare the global programme of gene expression in HTLV-positive, ATL-derived and HTLV-positive in vitro-transformed cell lines with that of uninfected primary CD4 T cells.
Elevated cyclic AMP levels in T lymphocytes transformed by human T-cell lymphotropic virus type 1.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Ikaros mediates gene silencing in T cells through Polycomb repressive complex 2.
Specimen part, Cell line
View SamplesThe Ikaros zink finger transcription factor is a critical regulator of the hematopietic system, and plays an important role in the regulation of the development and function of several blood cell lineages.
Ikaros mediates gene silencing in T cells through Polycomb repressive complex 2.
Specimen part
View Samples