Gene expression profiles of dasatinib-resistant and dasatinib-sensitive pancreatic cancer cell lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Chien W
PROVIDER: S-ECPF-GEOD-59357 | biostudies-other | 2015 Apr
REPOSITORIES: biostudies-other
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Project description:Gene profiles from three dasatinib-resistant and three dasatinib-sensitive pancreatic cancer cell lines were compared by microarray analysis.
2015-02-24 | GSE59357 | GEO
Project description:Gene profiles from three dasatinib-resistant and three dasatinib-sensitive pancreatic cancer cell lines were compared by microarray analysis. RNA from three dasatinib-resistant (MiaPaCa2, Panc1, SU8686) and three dasatinib-sensitive (Panc0504, Panc0403, Panc1005) pancreatic cancer cell lines were extracted. Biological triplicates were employed for each cell line. Complementary DNA microarray analysis was performed using Illumina Human HT-12 v4 BeadChip (Illumina, San Diego, CA) at the National University of Singapore Core Facility following the manufacturer’s instructions.
2015-02-24 | E-GEOD-59357 | biostudies-arrayexpress
Project description:Gene expression profiles of 5 cancer cell lines, including lung cancer (SBC-5 (duplicate samples), ACC-LC319/bone2, NCI-H1048); and breast cancer (ZR75.1, HCC1397) were analyzed. Cells were cultured following the guidelines published somewhere, and at confluent ~ 80% cells were extracted RNA for microarray analysis.
| S-ECPF-GEOD-40559 | biostudies-other
Project description:In order to develop targeted strategies for combating drug resistance it is essential to understand it's basic molecular mechanisms. In an exploratory study we have found several possible indicators of etoposide resistance operating in MCF7VP cells, including up-regulation of ABC transporter genes, modulation of miRNA, and alteration in copy numbers of genes.
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Project description:The total expression profiles of two medulloblastoma cell lines resistant to the preactivated form of cyclophosphamide (4-hydroperoxycyclophosphamide, 4-HC) were examined using the Affymetrix GeneChip U133A array. Our primary objective was to look for possible genes, other than the well-studied aldehyde dehydrogenases (ALDH) that may be involved in cyclophosphamide (CP) resistance in medulloblastomas. We present here the lists of the most highly upregulated [30 for D341 MED (4-HCR); 20 for D283 MED (4-HCR)] and downregulated [19 for D341 MED (4-HCR); 15 for D283 MED (4-HCR)] genes which may be involved in conferring CP-resistance to the two medullobalstoma cell lines. The lists of genes from the two sublines almost had no overlap, suggesting different mechanisms of CP-resistance. One of the most noteworthy upregulated gene is TAP1 [90-fold increase in D341 MED (4-HCR) relative to D341 MED]. TAP1, a protein belonging to the ABC transporter family is normally involved in major histocompatibility class I (MHC I) antigen processing. This suggests the possible role of multidrug resistance (MDR), albeit atypical (which means it does not involve the usual MDR1 and MRP glycoproteins), in medulloblastoma's CP-resistance. Apart from TAP1, a number of other genes involved in MHC1 processing were upregulated in D341 MED (4HCR). D341 MED (4-HCR) also had a 20-fold increase in the expression of the aldo-keto reductase gene, AKR1B10, which may deactivate the reactive cyclophosphamide metabolite, aldophosphamide. For D283 MED (4-HCR), the most notable increase in expression is that of ALDH1B1, a member of the aldehyde dehydrogenase (ALDH) family of proteins.
| S-EPMC3633091 | biostudies-literature
Project description:Testicular germ cell tumors (TGCTs) represent a well curable malignity due to their exceptional response to cisplatin (CDDP). Despite remarkable treatment results, approximately 5% of TGCT patients develop CDDP resistance and die. Exceptional curability makes TGCTs a highly valuable model system for studying the molecular mechanisms of CDDP sensitivity. Our study was aimed at revealing difference in gene expression between the CDDP-resistant and -sensitive TGCT cell lines, and hence at identifying candidate genes that could serve as potential biomarkers of CDDP response. Using gene expression array, we identified 281 genes that are differentially expressed in CDDP-resistant compared to -sensitive TGCT cell lines. The expression of 25 genes with the highest fold change was validated by RT-qPCR. Of them, DNMT3L, GAL, IGFBP2, IGFBP7, L1TD1, NANOG, NTF3, POU5F1, SOX2, WNT6, ZFP42, ID2, PCP4, SLC40A1 and TRIB3, displayed comparable expression change in gene expression array and RT-qPCR, when all CDDP-resistant TGCT cell lines were pairwise combined with all -sensitive ones. Products of the identified genes are pluripotency factors, or are involved in processes, such as cell metabolism, proliferation or migration. We propose that, after clinical validation, these genes could serve as prognostic biomarkers for early detection of CDDP response in TGCT patients.
| S-EPMC7771712 | biostudies-literature
Project description:BackgroundMicroRNAs (miRs) regulate gene expression through translation inhibition of target mRNAs. One of the most promising approaches for cancer therapy is through mimicking or antagonizing the action of miRs. In this report, we analyzed the miRnome profile of several human breast cancer cell lines to determine the influence of estrogen receptor (ER) silencing previously shown to result in epithelial to mesenchymal transition (EMT) and enhanced tumor invasion.MethodsMicroRNA extracted from MDA-MB-231 (de novo ER-) and ER-silenced (acquired ER-) pII and IM-26 or ER-expressing (YS1.2) siRNA transfected derivatives of MCF7 cells was deep sequenced on Illumina NextSeq500. Respective miRnomes were compared with edgeR package in R and Venny2.1 and target prediction performed with miRTarBase. Mimics and inhibitors of selected differentially expressed miRs associated with EMT mediators (miR-200c-3p targeting ZEB1, miR-449a targeting δ-catenin and miR-29a-3p) were transfected into pII cells and mRNA targets, as well as E-cadherin and keratin 19 (epithelial and mesenchymal markers respectively) were measured using taqman PCR.ResultsEach cell line expressed about 20% of the total known human miRnome; There was a high degree of similarity between the 3 tested ER-lines. Out of these expressed miRs, 50-60% were significantly differentially expressed between ER- and ER + lines. Transfection of miR-200c-3p mimic into pII cells down regulated ZEB1 and vimentin, and increased E-cadherin and keratin 19 with accompanying morphological changes, and reduced cell motility, reflecting a reversal back into an epithelial phenotype. On the other hand, transfecting pII with miR-449a inhibitor reduced cell invasion but did not induce EMT. Transfecting pII cell line with the mimic or inhibitor of miR-29a-3p showed no change in EMT markers or cell invasion suggesting that the EMT induced by loss of ER function can be reversed by blocking some but not just any random EMT-associated genes.ConclusionsThese data suggest that differences in miR expression can be exploited not only as mediators (using mimics) and targets (using miR antagonists) for general cancer therapies aimed at regulating either individual or multiple mRNAs, but also to re-sensitize endocrine resistant breast cancers by turning them back into a type that will be susceptible to endocrine agents.
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Project description:Numerous epithelial-to-mesenchymal transition (EMT)-promoting transcription factors have been implicated in tumorigenesis or metastasis, as well as chemoresistance of cancer. However, the underlying mechanism mediating these processes is unclear. Here we report that Foxq1, a forkhead box-containing transcription factor and EMT-inducing gene, promotes stemness traits and chemoresistance in mammary epithelial cells. We identify Twist1, Zeb2, and PDGFRα and β as Foxq1 downstream targets using an expression profiling assay. Further studies reveal that PDGFRα and β can be directly regulated by Foxq1, or indirectly through Twist1. Knockdown of both PDGFRα and β shows more significant effects on reversing Foxq1-promoted oncogenesis in vitro and in vivo than knockdown by either PDGFRα or β alone. PDGFRβ, but not PDGFRα, shows potent effects in reversing Foxq1-promoted stemness traits. Moreover, pharmacological inhibition or gene silencing of PDGFRs sensitize mammary epithelial cells to chemotherapeutic agents in vitro and in vivo. These findings collectively indicate PDGFRs as critical mediators underlying breast cancer tumorigenesis and chemoresistance driven by EMT promoting genes, which have potential clinical implications for cancer therapy. The purpose of these experiments is to investigate the downstream targets of several transcriptional factors including Foxq1 and IRX5. Another purpose is to compare the expression pattern between basal-like breast cancer cells including MDA-MB231, SUM159 and SUM1315.
| S-ECPF-GEOD-46834 | biostudies-other
Project description:The Src family of non-receptor tyrosine kinases are frequently activated in pancreatic ductal adenocarcinoma (PDAC), contributing to disease progression through downregulation of E-cadherin and induction of epithelial-to-mesenchymal transition (EMT). The purpose of this study was to examine the efficacy of Src kinase inhibition in restoring E-cadherin levels in PDAC. Immunohistochemical analysis of human PDAC samples showed Src activation is inversely correlated with E-cadherin levels. Protein and mRNA levels of E-cadherin, the gene expression of its various transcriptional repressors (Zeb1, Snail, Slug, LEF-1, TWIST), and changes in sub-cellular localization of E-cadherin/β-catenin in PDAC cells were characterized in response to treatment with the Src inhibitor, dasatinib (DST). DST repressed Slug mRNA expression, promoted E-cadherin transcription, and increased total and membranous E-cadherin/β-catenin levels in drug-sensitive PDAC cells (BxPC3 and SW1990), however no change was observed in drug-resistant PANC1 cells. BxPC3, PANC1, and MiaPaCa-2 flank tumor xenografts were treated with DST to examine changes in E-cadherin levels in vivo. Although DST inhibited Src phosphorylation in all xenograft models, E-cadherin levels were only restored in BxPC3 xenograft tumors. These results suggest that Src kinase inhibition reverses EMT in drug-sensitive PDAC cells through Slug-mediated repression of E-cadherin and identifies E-cadherin as potential biomarker for determining response to DST treatment.
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Project description:Resistance to endocrine therapy agents has presented a clinical obstacle in the treatment of hormone-dependent breast cancer. Our laboratory has initiated a study of microRNA regulation of signaling pathways that may result in breast cancer progression on aromatase inhibitors (AI). Microarray analysis of microRNA expression identified 115 significantly regulated microRNAs, of which 49 microRNAs were believed to be hormone-responsive. Within the AI-resistant cells, microRNAs were differentially expressed between the steroidal and non-steroidal AI-resistant lines. Also, a group of microRNAs were inversely expressed in the AI-resistant lines versus LTEDaro and tamoxifen-resistant. We focused our work on hsa-miR-128a which was hormone-responsive and up-regulated in the letrozole-resistant cell lines. Human miR-128a was shown to negatively target TGFBRI protein expression by binding to the 3’UTR region of the gene. Loss of TGFBRI resulted in compromised sensitivity to the growth inhibitory effects of TGFB in the letrozole-resistant lines. Inhibition of endogenous miR-128a resulted in re-sensitization of the letrozole-resistant lines to TGFB growth inhibitory effects. This data suggests that the hormone-responsive miR-128a can modulate TGFB signaling and survival of the letrozole-resistant cell lines. To our knowledge, this is the first study to address the role of microRNA regulation as well as TGFB signaling in AI-resistant breast cancer cell lines. We believe that in addition to estrogen-modulation of gene expression, hormone-regulated microRNAs may provide an additional level of post-transcriptional regulation of signaling pathways critically involved in breast cancer progression and AI-resistance. To look at microRNA expression profiles of breast cancer cell lines derived from MCF-7 cells that are resistant to endocrine therapy agents. MCF-7 cells that overexpress aromatase (MCF-7aro) were cultured long-term in the presence of endocrine therapy agents until cells acquired resistance. Three different aromatase inhibitors (letrozole, anastrozole or exemestane) were used, as well as the ER antagonist tamoxifen, or the hormone-free long-term estrogen deprived cells (LTED). Three replicates of the control cells (MCF-7aro) and all resistant cells were used for microarray experiments. Total of 23 samples were analyzed by microarray.
| S-ECPF-GEOD-17775 | biostudies-other