Conventional anti-cancer drug screening is typically performed in the absence of accessory cells (e.g. stromal cells) of the tumor microenvironment, which can profoundly alter anti-tumor drug activity. To address this major limitation, we have developed assays (e.g. the tumor cell-specific in vitro bioluminescence imaging (CS-BLI) assay) to selectively quantify tumor cell viability, in presence vs. absence of non-malignant stromal cells or drug treatment. These assays have allowed us to identify that neoplastic cells from diverse malignancies exhibit stroma-induced resistance to different anti-tumor agents. In this analysis, we evaluated the molecular changes triggered in myeloma cells by their in vitro interaction with stromal cells. The transcriptional profile of 3 human multiple myeloma (MM) cell lines (MM.1S, MM.1R, INA-6) co-cultured with stromal cells vs. when cultured alone was characterized by oligonucleotide microarray analysis, using the human U133 plus 2.0 Affymetrix GeneChip.
Tumor cell-specific bioluminescence platform to identify stroma-induced changes to anticancer drug activity.
Cell line
View SamplesEstrogen signaling pathway is critical for breast cancer development and has remained the major adjuvant therapeutic target for this disease. Tamoxifen has been used in clinic for many years to treat ER-positive breast cancer. However a great many (30%) suffer relapse due to drug resistance. In this study, the bromodomain inhibitor JQ1 was found to down-regulate ERalpha gene expression and have anti-tumor effect in cultured tamoxifen-resisant breast cancer cells.
An epigenomic approach to therapy for tamoxifen-resistant breast cancer.
Cell line, Treatment
View SamplesWe examine the role of Klf6 in oligodendrocyte progenitor cells and determine that Klf6 acts as a gp130-sensitive transactivator of the nuclear import factor importin-a5 (Impa5), a key controller of nuclear trafficking in oligodendrocytes. Overall design: Examination of expression profiles of 2 different cell stages exposed to siRNA vs. control
The Transcriptional Activator Krüppel-like Factor-6 Is Required for CNS Myelination.
Specimen part, Cell line, Subject
View SamplesGlobal gene expression data from 7-day old light-grown liquid cultured seedlings treated with or without auxin (5M IAA) for 2 h.
AUXIN RESPONSE FACTOR 2 (ARF2): a pleiotropic developmental regulator.
No sample metadata fields
View SamplesGlobal gene expression data from 7-day old light-grown liquid cultured seedlings treated with or without auxin (5M IAA) for 2 h. Columbia (WT) and Auxin response factor 2 (ARF2) T-DNA insertion mutant (arf2-6 ) were used for this study. Each experimental condition has three true replicates for a total of 12 hybridizations.
AUXIN RESPONSE FACTOR 2 (ARF2): a pleiotropic developmental regulator.
No sample metadata fields
View SamplesThe androgen receptor (AR) is a key driver of prostate cancer (PC), even in the state of castration-resistant PC (CRPC), and frequently even after treatment with second-line hormonal therapies such as abiraterone and enzalutamide. The persistence of AR activity via both ligand-dependent and ligand-independent (including constitutively active AR splice variants) mechanisms highlights the unmet need for alternative approaches to block AR signaling in CRPC. We investigated the transcription factor GATA2 as a regulator of AR signaling and a novel therapeutic target in PC. We demonstrate that GATA2 directly promotes AR expression (both full-length and splice variant), resulting in a strong positive correlation between GATA2 and AR expression in PC (cell lines and patient specimens). Conversely, GATA2 expression is repressed by androgen and AR, suggesting a negative feedback regulatory loop that, upon androgen deprivation, derepresses GATA2 to contribute to AR overexpression in CRPC. Simultaneously, GATA2 is necessary for optimal transcriptional activity of AR (both full-length and splice variant). GATA2 co-localizes with AR and FOXA1 on chromatin to enhance recruitment of steroid receptor coactivators (SRCs) and formation of the transcriptional holocomplex. In agreement with these important functions, high GATA2 expression and transcriptional activity predicted for worse clinical outcome in PC patients. A GATA2 small molecule inhibitor suppressed the expression and transcriptional function of AR (both full-length and splice variant) and exerted potent anticancer activity against PC cell lines. We propose pharmacological inhibition of GATA2 as a first-in-field approach to target AR expression and function and improve outcomes in CRPC.
GATA2 facilitates steroid receptor coactivator recruitment to the androgen receptor complex.
Cell line
View SamplesWe previously found a short sleeper mutant, fmn, and identified its mutation in the dopamine transporter gene. In an attempt to discover additional sleep related genes in Drosophila, we carried out a microarray analysis comparing mRNA expression in heads of fmn and control flies and found differentially expressed genes.
The NMDA Receptor Promotes Sleep in the Fruit Fly, Drosophila melanogaster.
Sex, Specimen part
View SamplesThe Arabidopsis thaliana NAC domain transcription factor, VASCULAR-RELATED NAC-DOMAIN7 (VND7), acts as a key regulator of xylem vessel differentiation. In order to identify direct target genes of VND7, we performed global transcriptome analysis using Arabidopsis transgenic lines in which VND7 activity could be induced post-translationally. This analysis identified 63 putative direct target genes of VND7, which encode a broad range of proteins, such as transcription factors, IRREGULAR XYLEM proteins and proteolytic enzymes, known to be closely associated with xylem vessel formation. Recombinant VND7 protein binds to several promoter sequences present in candidate direct target genes: specifically, in the promoter of XYLEM CYSTEINE PEPTIDASE1, two distinct regions were demonstrated to be responsible for VND7 binding. We also found that expression of VND7 restores secondary cell wall formation in the fiber cells of inflorescence stems of nst1nst3 double mutants, as well as expression of NAC SECONDARY WALL THICKENING PROMOTING FACTOR3 (NST3, however, the vessel-type secondary wall deposition was observed only as a result of VND7 expression. These findings indicated that VND7 upregulates, directly and/or indirectly, many genes involved in a wide range of processes in xylem vessel differentiation, and that its target genes are partially different from those of NSTs.
VASCULAR-RELATED NAC-DOMAIN7 directly regulates the expression of a broad range of genes for xylem vessel formation.
Age, Specimen part, Treatment
View SamplesHsp90 is critical for regulation of the phenotype and functional activity of human T lymphocytes and natural killer (NK) cells.
Heat shock protein 90 is critical for regulation of phenotype and functional activity of human T lymphocytes and NK cells.
Specimen part, Treatment
View SamplesIn this study, we sought to establish the usefulness of LCM on cDNA microarray analysis. We reported that LCM samples improved the sensitivity of detection of differentially expressed genes over conventional bulk tissue analysis. We also provided the new information of chemokine and its receptor interaction within psoriatic lesional skin.
Combined use of laser capture microdissection and cDNA microarray analysis identifies locally expressed disease-related genes in focal regions of psoriasis vulgaris skin lesions.
Specimen part, Subject
View Samples