Project description:UFH-001 cells, a newly isolated breast cancer line, have an STR profile that is most similar to that of the control MCF10A cells. Yet, the UFH-001 line is tumor forming with a triple negative phenotype. These cells have a unique transcriptome profile associated numerous breast cancer marker genes. We used microarrays to detail the global programme of gene expression underlying the metastatic behavior of the UFH-001 cells compared to the MCF10A cells.
Project description:We wanted to know how introduction of H1047R oncogenic mutation of PIK3CA (p110a subunit of PI3K) in HER2-overexpressing MCF10A human non-transformed mammary epitheial cell lines introduces change in gene expression levels. Our control was HER2-overexpressing MCF10A cell line with wild-type (WT) PIK3CA. Mutated oncogene-induced gene expression signature was measured and compared with that induced by the WT oncogene from cell lines harvested at 70-80% confluency.
Project description:In pediatric glioma cell lines, treatment with ICG-001 had no inhibitory effect on canonical Wnt-target genes but induced significant up regulation of various known β-catenin target genes in both cell lines and top 20 GO-annotations of down-regulated genes by ICG-001 were associated with biosynthetic and metabolic processes and cell cycle division processes. Pediatric cell lines were treated with ICG-001 or DMSO for 48h
Project description:We examined the effects of ICG-001 on gene expression in Mel202 uveal melanoma (UM) cells. ICG-001 exerted strong antiproliferative activity against UM cells, leading to cell cycle arrest, apoptosis, and inhibition of migration. Global gene expression profiling revealed strong suppression of genes associated with cell cycle proliferation, DNA replication, and G1/S transition. Gene set enrichment analysis revealed that ICG-001 suppressed Wnt, mTOR, and MAPK signaling. Strikingly, ICG-001 suppressed the expression of genes associated with UM aggressiveness, including CDH1, CITED1, EMP1, EMP3, SDCBP, and SPARC. Notably, the transcriptomic footprint of ICG-001, when applied to a UM patient dataset, was associated with better clinical outcome. Lastly, ICG-001 exerted anticancer activity against a UM tumor xenograft in mice.
Project description:The CREB binding protein inhibitor ICG-001 suppresses pancreatic cancer growth We used microarrays to detail global gene expression changes in the pancreatic cancer cell line AsPC1 following treatment with ICG-001 or siRNA-mediated knockdown of CTNNB1 (beta-catenin)
Project description:In pediatric glioma cell lines, treatment with ICG-001 had no inhibitory effect on canonical Wnt-target genes but induced significant up regulation of various known β-catenin target genes in both cell lines and top 20 GO-annotations of down-regulated genes by ICG-001 were associated with biosynthetic and metabolic processes and cell cycle division processes.
Project description:To inhibitors for ADAR1 and a strong rationale for the development of ADAR1 p150 inhibitors for cancer immunotherapy Here, we describe AVA-ADR-001, a potential first-in-class small molecule inhibitor of ADAR1 p150 targeting the Z alpha domain. AVA-ADR-001 binds specifically to the Z alpha domain of ADAR1 p150 as confirmed by fluorescence spectroscopy and showed significant interferon induction in THP1 macrophages, which have high ADAR1 p150 expression compared with monocytes. Proteomics and transcriptomics analysis revealed significant upregulation of interferon signaling upon treatment with AVA-ADR -001. Interestingly, activation of interferon signaling resulted in AVA-ADR-001 induced cell killing in ADAR1-independent cell lines. In addition, treatment with AVA-ADR -001 resulted in significant activation of PKR, which may explain the decreased cell proliferation. Finally, AVA-ADR-001 showed superior anti-tumor efficacy compared to anti-PD1 in an in vivo tumor efficacy study and has a moderately synergistic effect when combined. Overall, this study reveals that ADAR1 p150 inhibition by AVA-ADR-001 exerts a multipronged impact on anti-tumor efficacy mediated by immune cells, accumulation of interferons and activation of PKR, resulting in protein translation inhibition and cell proliferation arrest.
Project description:The CREB binding protein inhibitor ICG-001 suppresses pancreatic cancer growth We used microarrays to detail global gene expression changes in the pancreatic cancer cell line AsPC1 following treatment with ICG-001 or siRNA-mediated knockdown of CTNNB1 (beta-catenin) AsPC1 cells were treated with 10uM ICG-001 or vehicle control (DMSO) for either 6 hours or 24 hours. AsPC-1 cells were also separately transfected with 20nM control siRNA or CTNNB1 siRNA for 48 hours. RNA was extracted at these time points for hybridization to Affymetrix microarrays
Project description:To characterize genomic instability in breast cancer progression, we examined copy number loss and copy number gain in the MCF10A series of cell lines.