Project description:RNA sequencing analysis to compare parental colorectal cancer cell lines and their selumetinib-resistant derivatives and identify expression changes and/or mutations that might contribute to resistance
Project description:Copy number analysis to compare parental colorectal cancer cell lines and their selumetinib-resistant derivatives and identify gene copy changes that might contribute to resistance
Project description:We performed Next Generation Sequencing of normal human intestinal epithelial cell lines, CRC cell lines and CRC cell lines with hypoxia treatment to identify the differentially expressed non-coding RNAs.
Project description:Anti-tumor effect of the combination between 5-FU and selumetinib was treatment schedule-dependent in BRAF or KRAS mutant CRC cells. Treatment of 5-FU for 2 days followed by selumetinib for another 2 days exhibited synergism for cell viability, whereas single or reversely combined treatment showed antagonism Microarray analysis revealed the distinct groups of genes underlying the efficacy for schedule-dependent treatment.
Project description:CGH profiling of M249 melanoma cell line treated with step-wise increasing Vemurafenib and Selumetinib to develop resistance (VSR). The resistance mechanims was through BRAF amplification in double minute (DM) format. The control cell line is untreated M249.
Project description:MDA231, BT549, and SUM159PT basal-like breast cancer cell lines were transfected with non-targeting siRNA (siCONTROL), siRNA targeting DUSP4 (siDUSP4), or siCONTROL + 4 or 24 hr of 1uM selumetinib. Cells were harvested at 96 hr post-siRNA transfection. Data were Log2 RMA normalized. We sought to identify changes in gene expression after MEK inhibition, or after loss of DUSP4 function in breast cancer cell lines.
Project description:Background: In vitro models are an essential tool towards understanding the molecular characteristics of colorectal cancer (CRC) and the testing of therapies for CRC. To this end we established 21 novel CRC cell lines of which six were derived from liver metastases. Extensive genetic, genomic, transcriptomic and methylomic profiling was performed in order to characterize these new cell lines and all data is made publically available. Additionally, sensitivity of oxaliplatin was tested as a measure for chemotherapy resistance. Results: DNA copy-number alterations (CNA) were compared between primary and metastasis derived cell lines. In concordance with previous studies copy-number gain of chr20, and loss of chr8p were found highly specific for liver metastases. Previously reported BRAF-mutation associated DNA methylation profiles could be validated on the genome-wide DNA methylation profiles of these cell lines. 47.6% of the loci previously reported to associate with BRAF mutation status were reproduced in this dataset. When examining the gene expression profiles in conjunction with these DNA methylation results, we identified 20 genes of which the gene expression correlated with the DNA methylation status, including MEIS1, LRAT and STC2. These genes have previously been reported to be subject to transcriptional regulation through DNA hypermethylation, validating our approach. Conclusions: By combining mutation profiles with CNA and gene expression profiles we constructed an overview of the alterations in the major CRC-related signalling pathways. The mutation profiles, along with the genome, transcriptome and methylome data of these cell lines will be made publically available . This combined dataset puts these cell lines among the best characterized CRC cell lines, allowing researchers to select appropriate cell line models for their particular experiment, making optimal use of these novel cell lines as in vitro model for CRC. 21 CRC cell lines were analyzed