Effect of continued exposure to drugs on gene expression in human pancreatic cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE216038 | GEO | 2025/10/17
REPOSITORIES: GEO
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Project description:Pancreatic ductal adenocarcinoma (PDAC) has a bad prognosis, a fast progression and is difficult to treat, highlighting the need for new therapeutic targets. Aggressive tumors mostly show Epithelial-to-Mesenchymal Transition (EMT). Protein phosphatase type 2A (PP2A) plays a central role in processes of cell survival and proliferation, but the link with EMT and tumor progression is largely unknown. Therefore, we examined expression of a PP2A gene set in five datasets of human PDAC and their association with an aggressive phenotype. Two datasets included PDAC tumor samples and normal pancreatic tissue. In two other datasets, the samples could be classified into clinical/molecular subtypes of EMT-high/aggressive and EMT-low/moderate PDAC. Spearman correlation, hierarchical clustering and ROC-analysis were performed. EMT was also quantified using weighted expression of 8 marker genes. In each study we observed that, compared to normal tissue, (advanced) tumor stage positively and significantly correlated with EMT. EMT-high PDAC showed suppression of PPP2R1B and PPP2R2D expression and upregulation of PPP2R3C, PPP2R5E, STRN, STRN3 and PPP2R2A. A strong link was further found for upregulation of endogenous inhibitors of PP2A (KIAA1524/CIP2A, ARPP19, TIPRL and PPME1) with advanced PDAC. ROC-curve indicates that high expression of PP2A-inhibitors are predictors of aggressive PDAC. This was further investigated in a cell line model of Panc-1 cells made resistant to the PP2A-inhibitor Okadaic acid. Gene expression was determined in cells exposed for 24 hours and resistant cells. In summary, we demonstrate an important association of PP2A inhibition with EMT in advanced human pancreatic cancer. We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different cells.
2023-05-16 | GSE216036 | GEO
Project description:The incidence for pancreatic ductal adenocarcinoma (PDAC) is rising which has a low survival rate. In cancer, Epithelial-to-Mesenchymal transition (EMT) contribute to an aggressive phenotype. Protein Phosphatase Type 2A (PP2A) are initially regarded as tumor suppressors, the connection with EMT in patients is uncertain. We investigated the relation of a ‘PP2A’ gene signature (en-compassing catalytic, structural and regulatory subunits; and endogenous PP2A inhibitors and activators) with EMT in PDAC patients. We could demonstrate a link between PDAC and EMT in four patient datasets using datamining, correlation study and gene set analysis. Furthermore, we identified a strong association of PP2A with EMT in advanced pancreatic cancer patients and in particular a significant upregulation of PP2A inhibitor genes in aggressive/EMT-high PDAC. In vitro, pharmacological inhibition of PP2A through Okadaic acid induced EMT in human pancreatic cells. Two different cell models were developed and their morphology, gene and protein expression determined. In the more advanced OA-induced EMT model (OA7G), statistical changes in proteins of natural PP2A-inhibitors was observed and this requires further investigations. Translationally, these observations indicate that PP2A could be a central factor in cancer and it is therefore attractive to test compounds that can target PP2A enzyme activity in PDAC.
2023-07-20 | PXD037976 | Pride
Project description:TGF-beta treatment of Panc-1 pancreatic adenocarcinoma cell line on Affymetrix HG_U133_plus_2 arrays; triplicate experiments. The goal of the experiment is to profile temporal gene expression changes during TGF-beta-induced epithelial-mesenchymal transition (EMT). During EMT cancer cells lose their epithelial specifc proteins and gain mesenchymal proteins to acquire migratory and invasive phenotype essential for metastasis. Human Panc-1 pancreatic adenocarcinoma cell line was treated with 5 ng/mL TGF-beta for 48 h to induce EMT. The experiment was repeated 3 times. Samples were assayed using Affymetrix HG_U133_plus_2 arrays with 54675 probe-sets, using standard techniques. Human Panc-1 pancreatic adenocarcinoma cell line was treated with 5 ng/mL TGF-beta for 48 h. The experiment was repeated 3 times. Samples were assayed using Affymetrix HG_U133_plus_2 arrays with 54675 probe-sets, using standard techniques.
2010-09-03 | E-GEOD-23952 | biostudies-arrayexpress
Project description:TGF-beta treatment of Panc-1 pancreatic adenocarcinoma cell line on Affymetrix HG_U133_plus_2 arrays; triplicate experiments. The goal of the experiment is to profile temporal gene expression changes during TGF-beta-induced epithelial-mesenchymal transition (EMT). During EMT cancer cells lose their epithelial specifc proteins and gain mesenchymal proteins to acquire migratory and invasive phenotype essential for metastasis. Human Panc-1 pancreatic adenocarcinoma cell line was treated with 5 ng/mL TGF-beta for 48 h to induce EMT. The experiment was repeated 3 times. Samples were assayed using Affymetrix HG_U133_plus_2 arrays with 54675 probe-sets, using standard techniques.
2010-09-03 | GSE23952 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous cancer in which differences in survival rates might be related to a variety in gene expression profiles. Although the molecular biology of PDAC begins to be revealed, genes or pathways that specifically drive tumour progression or metastasis are not well understood. Therefore, we performed microarray analyses on whole-tumour samples of 2 human PDAC subpopulations with similar clinicopathological features, but extremely distinct survival rates after potentially curative surgery, i.e., good outcome (OS and DFSM-bM-^@M-^I>M-bM-^@M-^I50M-bM-^@M-^Imonths) versus bad outcome (OSM-bM-^@M-^I<M-bM-^@M-^I19M-bM-^@M-^Imonths and DFSM-bM-^@M-^I<M-bM-^@M-^I7M-bM-^@M-^Imonths). Additionally, liver- and peritoneal metastases were analysed and compared to primary cancer tissue. The integrin and ephrin receptor families were upregulated in all PDAC samples, irrespective of outcome, supporting an important role of the interaction between pancreatic cancer cells and the surrounding desmoplastic reaction in tumorigenesis and cancer progression. Moreover, some components, such as ITGB1 and EPHA2, were upregulated in PDAC samples with a poor outcome, Additionally, overexpression of the non-canonical Wnt/M-NM-2-catenin pathway and EMT genes in PDAC samples with bad versus good outcome suggests their contribution to the invasiveness of pancreatic cancer, with M-NM-2-catenin being also highly upregulated in metastatic tissue. Thus, we conclude that components of the integrin and ephrin pathways and EMT-related genes might serve as molecular markers in pancreatic cancer as their expression seems to be related with prognosis. Microarray analysis was performed on 'Good' and 'Bad' patient samples (samples with similar pathological characteristics were chosen based on the definition of the 2 diverse survival outcome groups and the required RIN values above 7.1), on surrounding non-tumoural pancreatic control samples, liver metastasis (LM) and peritoneal metastasis (PM). Comparisons between good vs. control, bad vs. control, good vs. bad, and primary pancreatic cancer versus metastasis were performed.
2013-01-09 | E-GEOD-42952 | biostudies-arrayexpress
Project description:Epithelial splicing regulatory proteins (ESRPs) are splicing regulators known to play a critical role in epithelial-mesenchymal transition (EMT) and the progression of various cancers, including pancreatic ductal adenocarcinoma (PDAC). Numerous cancer-related genes, such as CD44, FGFR2, and CDNND1, are spliced by ESRP1 and 2 with differential expression of variants. Here, we analyzed ESRP1 and 2 overexpressing pancreatic cancer cells, PANC-1 and MIA-PaCa2, and discovered splicing targets of ESRPs.
2025-08-25 | GSE275607 | GEO
Project description:Purpose: Chemotherapy is pivotal in the multimodal treatment of pancreatic cancer patients. In recent years, technical advances have developed experimental methods that unveiled a high degree of inter- and intratumoral heterogeneity in pancreatic cancer. We hypothesized that intratumoral heterogeneity (ITH) impacts response to gemcitabine treatment and demands specific targeting of resistant subclones. Experimental Design: We addressed the effect of ITH on response to gemcitabine treatment using single cell-derived cell lines (SCDCL) from the classical-like cell line BxPC3 and the basal-like cell line Panc-1 which were analyzed by mRNA-seq and mass spectrometry. Results: Individual SCDCLs of the parental tumor cell populations of BxPC3 and Panc-1 showed considerable heterogeneity in response to gemcitabine. Unsupervised principal component analysis (PCA) including the 1,000 most variably expressed genes showed a clustering of the SCDCLs according to their respective sensitivity to gemcitabine treatment for BxPC3, while this clustering was less clear for Panc-1. In BxPC3 SCDCLs, enriched signaling pathways EMT, TNF signaling via NfKB, and IL2STAT5 signaling correlated with more resistant behavior to gemcitabine. In Panc-1 SCDCLs MYC targets V1 and V2 as well as E2F targets were associated with stronger resistance to gemcitabine. Feature extraction of proteomes again identified less proteins whose expression was associated with the response of individual SCDCLs in Panc-1 compared to BxPC3. Based on molecular profiles, we could show that the gemcitabine-resistant SCDCLs of both BxPC3 and Panc-1 are more sensitive to the BET inhibitor JQ1 compared to the respective gemcitabine-sensitive SCDCLs. Conclusions: Our model system of SCDCLs identified gemcitabine-resistant subclones within a parental tumor population and provides evidence for the critical role of ITH for treatment response in pancreatic cancer. Through molecular profiling, we identified specific signaling pathways and protein signatures that might help to explain the differential response to treatment among clones. We exploited these molecular differences for an improved and more targeted therapy of resistant subclones of a heterogeneous tumor.
2023-09-19 | PXD042256 | Pride
Project description:Protein arginine methylation has been established an essential protein modification regulating cancer initiation and progression, but its implications in PDAC (Pancreatic ductal adenocarcinoma) still remains poorly elucidated. In this study, we characterized ADMA (asymmetric dimethylarginine)-bearing peptides in human pancreatic ductal epithelium cell line HPDE6c7 and PDAC cell line PANC-1 by a label-free quantitative proteomics combined with affinity purification.
2020-02-18 | PXD017577 |
Project description:No reliable predictors of susceptibility to gemcitabine chemotherapy exist in pancreatic ductal adenocarcinoma. MicroRNAs (miR) are epigenetic gene regulators with tumorsuppressive or oncogenic roles in various carcinomas. This study assesses chemoresistant PDAC for its specific miR expression pattern. Gemcitabine-resistant variants of PANC-1, a mutant p53 human pancreatic adenocarcinoma cell line, were established. MicroRNA screening was investigated by microarray.
2015-11-03 | GSE74562 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous cancer in which differences in survival rates might be related to a variety in gene expression profiles. Although the molecular biology of PDAC begins to be revealed, genes or pathways that specifically drive tumour progression or metastasis are not well understood. Therefore, we performed microarray analyses on whole-tumour samples of 2 human PDAC subpopulations with similar clinicopathological features, but extremely distinct survival rates after potentially curative surgery, i.e., good outcome (OS and DFS > 50 months) versus bad outcome (OS < 19 months and DFS < 7 months). Additionally, liver- and peritoneal metastases were analysed and compared to primary cancer tissue. The integrin and ephrin receptor families were upregulated in all PDAC samples, irrespective of outcome, supporting an important role of the interaction between pancreatic cancer cells and the surrounding desmoplastic reaction in tumorigenesis and cancer progression. Moreover, some components, such as ITGB1 and EPHA2, were upregulated in PDAC samples with a poor outcome, Additionally, overexpression of the non-canonical Wnt/β-catenin pathway and EMT genes in PDAC samples with bad versus good outcome suggests their contribution to the invasiveness of pancreatic cancer, with β-catenin being also highly upregulated in metastatic tissue. Thus, we conclude that components of the integrin and ephrin pathways and EMT-related genes might serve as molecular markers in pancreatic cancer as their expression seems to be related with prognosis.
2013-01-09 | GSE42952 | GEO