ARC (NSC 188491, SMA-491), 4-amino-6-hydrazino-7-beta-d-ribofuranosyl-7H-pyrrolo-(2,3-d)-pyrimidine-5-carboxamide, is a nucleoside analog with profound in vitro anti-cancer activity. First identified in a high-throughput screen for inhibitors of p21 mRNA expression, subsequent experiments showed that ARC also repressed expression of hdm2 and survivin, leading to its classification as a global inhibitor of transcription 1. The following Hu U133 plus 2.0 arrays represent single time point (24 hour) gene expression analysis of transcripts altered by ARC treatment. Arrays for the other compounds (sangivamycin and doxorubicin) are included as comparators.
ARC (NSC 188491) has identical activity to Sangivamycin (NSC 65346) including inhibition of both P-TEFb and PKC.
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View SamplesGene expression analysis under normal culture conditions (RPMI-10%FBS) and at optimal cell densities.
Low-risk susceptibility alleles in 40 human breast cancer cell lines.
Cell line
View SamplesDevelopment of LNA gapmers, antisense oligonucleotides used for efficient inhibition of target RNA expression, is limited by non-target mediated hepatotoxicity issues. In the present study, we investigated hepatic transcription profiles of mice receiving non-toxic and toxic LNA gapmers after a single and repeat administration.
Comparison of hepatic transcription profiles of locked ribonucleic acid antisense oligonucleotides: evidence of distinct pathways contributing to non-target mediated toxicity in mice.
Sex, Specimen part
View SamplesThis research identifies a novel protein required for paramutation at the maize purple plant1 locus. This 'required to maintain repression2' (RMR2) protein represents the founding member of a plant-specific clade of hypothetical proteins. We show that RMR2 is required for transcriptional repression at the Pl1-Rhoades haplotype, for accumulation of 24 nt RNA species, and for maintenance of a 5-methylcytosine pattern distinct from that maintained by RNA polymerase IV. Genetic tests indicate that RMR2 is not required for paramutation occurring at the red1 locus. These results distinguish the paramutation-type mechanisms operating at specific haplotypes. The RMR2 clade of proteins provides a new entry point for understanding the diversity of epigenomic control operating in higher plants. Overall design: Examination of small RNAs using Illumina's sequencing-by-synthesis (SBS) platform to deep sequence small RNA libraries made from the 4-cm cobs of rmr2 mutant and non-mutant siblings.
required to maintain repression2 is a novel protein that facilitates locus-specific paramutation in maize.
Specimen part, Subject
View SamplesXenograft models remain a cornerstone technology in the development of anti-cancer agents. The ability of immunocompromised rodents to support the growth of human tumors provides an invaluable transition between in vitro testing and clinical trials. Therefore, approaches to improve model selection are required. In this study, cDNA microarray data was generated for a collection of xenograft models at in vivo passages 1, 4 and 10 (P1, P4 and P10) along with originating cell lines (P0). These data can be mined to determine transcript expression 1) relative to other models 2) with successive in vivo passage and 3) during the in vitro (P0) to in vivo (P1) transition.
Gene expression profiling of 49 human tumor xenografts from in vitro culture through multiple in vivo passages--strategies for data mining in support of therapeutic studies.
No sample metadata fields
View SamplesTranscriptomic studies of human tumor xenografts are complicated by the presence of murine cellular mRNA. As such, it is useful to know the extent to which mouse mRNA cross-hybridizes to any given array platform. In this study, murine cDNA samples from diverse sources were hybridized to Affymetrix Human Genome U133 Plus 2.0 Arrays. In this regard it is possible to identify specific probes that are potential targets of cross-species interference.
Gene expression profiling of 49 human tumor xenografts from in vitro culture through multiple in vivo passages--strategies for data mining in support of therapeutic studies.
Specimen part, Cell line
View SamplesGermline BRCA1 or BRCA2 mutations (mtBRCA1 and mtBRCA2) dramatically increase risk for high-grade serous ovarian cancer (HGSOC), the most commonly diagnosed histotype. Other risk factors for this cancer, which originates primarily in the distal fallopian tube epithelium (FTE), implicate ovulation. To test whether mtBRCA1 or mtBRCA2 FTE cells respond differently to peri-ovulatory follicular fluid (FF) exposure than control patient FTE, gene expression profiles from primary FTE cultures were compared at baseline, 24h after FF exposure, and 24h after FF replacement with culture medium. Hierarchical clustering revealed both FF exposure and BRCA mutation status affect gene expression, with BRCA1 mutation having the greatest impact. Analysis revealed increased NFB and EGFR signaling at baseline, with increased interferon signaling after recovery from FF exposure in mtBRCA1 samples. Inhibition of EGFR signaling and ISGylation by increased BRCA1 expression was verified in an immortalized FTE cell line, OE-E6/E7, stably transfected with BRCA1. Suppression of ISG15 and ISGylated protein levels by BRCA1 expression was found to be mediated by decreased NFB signaling and was transiently suppressed by FF exposure. This study demonstrates increased NFB signaling associated with decreased BRCA1 expression resulting in increased ISG15 and ISGylation following FF exposure, which could represent potential targets for chemoprevention.
BRCA1 Mutation Status and Follicular Fluid Exposure Alters NFκB Signaling and ISGylation in Human Fallopian Tube Epithelial Cells.
Specimen part, Time
View SamplesETS1 and RAS/ERK regulate a common gene expression program in establishing enviroment suitable for prostate cancer cell migration. Overall design: mRNA profiles of luciferase knockdown (WT), ETS1 knockdown, and U0126 treated DU145 cells were generated using deep sequencing, in triplicate, using Illumina HiSeq. Knockdowns were stable shRNA expression from a lentiviral construct selected with puromycin.
Interaction with ZMYND11 mediates opposing roles of Ras-responsive transcription factors ETS1 and ETS2.
No sample metadata fields
View SamplesWe measured gene expression of D. melanogaster female heads and abdomens after mating with males from six populations evolved under either enforced monogamy (no male-male competition, 3 populations) or sustained polygamy (intense male-male competition, 3 populations). Overall design: Three samples of virgin female heads and six samples of mated female heads (one each per male evolved population, of which there are three monogamous and three polygamous), for nine libraries. Also, three samples of virgin female abdomens and six samples of mated female abdomens (one each per male evolved population, of which there are three monogamous and three polygamous), for nine libraries. In total, eighteen libraries sequenced in 8 lanes.
Sexual conflict drives male manipulation of female postmating responses in <i>Drosophila melanogaster</i>.
Sex, Specimen part, Subject
View SamplesLoss of E2F transcription factos alters metastatic capacity of MMTV-PyMT tumors.
Histological subtypes of mouse mammary tumors reveal conserved relationships to human cancers.
Disease
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