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.
Project description:Pancreatic ductal adenocarcinoma, caused by activating mutation in K-Ras, is an aggressive malignancy due to its early invasion and matastasis. Ral GTPases, negatively regulated by RalGAP, are activated downstream of Ras and play a crucial role in development and progression of pancreatic ductal adenocarcinoma. However, the underlying mechanisms remain unclear. We used microarrays to detail the global programme of gene expression underlying the human pancreatic ductal adenocarcinoma cell line, MIA PaCa-2 with RalGAPβ deficiency or not, and identified distinct classes of Ral activation-related mRNA.
Project description:Constitutive Kras and NF-kB activation is identified as signature alterations in human pancreatic ductal adenocarcinoma (PDAC). Here, we report that pancreas-targeted IKK2/beta inactivation inhibited NF-kB activation and completely suppressed PDAC development. Our findings demonstrated that NF-kB is required for development of pancreatic ductal adenocarcinoma that was initiated by Kras activation. Pancreatic tissue from 4 groups of mice were used in this project: (1) the pancreas normal appearance of Pdx1-cre;KrasLSL-G12D;IKK2/beta mice, (2) the normal pancreas of Pdx1-cre;KrasLSL-G12D mice, (3) the pancreatic lesion of pancreatic intraepithelial neoplasia (PanIN) of Pdx1-cre;KrasLSL-G12D mice, and (4) the pancreatic lesion of PDAC of Pdx1-cre;KrasLSL-G12D mice. Each group included three mice. RNA samples from mouse pancreas were hybridized on GeneChip Mouse Gene 1.0 ST arrays (Affymetrix). Group (1) and group (2) were compared, and group (2), group (3) and group (4) were compared.
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.
Project description:Lysosomes were immuno-isolated from HEK293T cells and PaTu8988T pancreatic ductal adenocarcinoma cells and analyzed by mass spectrometry based proteomics. Three independent biological replicates for each cell line is provided.
