Project description:Tamoxifen is the most widely administered adjuvant first-line hormone therapy for Estrogen receptor α (ERα) positive breast cancer patients. However, one from three patients will develop resistance, while the underlying molecular mechanisms are currently unclear. Recent studies reported that abnormal expression of miRNAs played a role in cancer progress. To study the potential function of miRNAs in tamoxifen resistance, Affymetrix GeneChip® miRNA 3.0 microarray was employed to identify differentially expressed miRNAs between tamoxifen sensitive MCF7 parent (MCF7-Pa) cells and induced resistant (MCF7-Re) cells.
Project description:The overarching goal of this study was to explore the antitumor activity of Z-endoxifen, a tamoxifen metabolite, with first-line endocrine therapies tamoxifen and letrozole in the letrozole-sensitive MCF7 aromatase expressing model (MCF7AC1), and with second-line endocrine therapies including tamoxifen, fulvestrant, exemestane, and exemestane plus everolimus, in letrozole-resistant MCF7 model (MCF7LR) in vivo. We used microarray to identify genes that are commonly and differently reguated by Z-endoxifen and tamoxifen treatments in the letrozole-resistant MCF7LR tumors.
Project description:Purpose: The present study provides the firstly large-scale characterization of miRNAs in Tetranychus cinnabarinus and the comparison between fenpropathrin resistant and susceptible strains gives a clue on study how miRNA involving in fenpropathrin resistance Methods: Using Illumina sequencing to identify the differentially expressed miRNAs between the fenpropathrin resistant and susceptible strains of Tetranychus cinnabarinus Results: 12 miRNAs that were expressed significantly differently were identified between thethe fenpropathrin resistant and susceptible strains of Tetranychus cinnabarinus
Project description:Resistance to tamoxifen in breast cancer patients is a serious therapeutic problem and major efforts are underway to understand underlying mechanisms. Resistance can be either intrinsic or acquired. We derived a series of subcloned MCF7 cell lines that were either highly sensitive or naturally resistant to tamoxifen and studied the factors that lead to drug resistance. Gene-expression studies revealed a signature of 67 genes that differentially respond to tamoxifen in sensitive vs. resistant subclones, which also predicts disease-free survival in tamoxifen-treated patients. High-throughput cell-based screens, in which >500 human kinases were independently ectopically expressed, identified 31 kinases that conferred drug resistance on sensitive cells. One of these, HSPB8, was also in the expression signature and, by itself, predicted poor clinical outcome in one cohort of patients. Further studies revealed that HSPB8 protected MCF7 cells from tamoxifen and blocked autophagy. Moreover, silencing HSBP8 induced autophagy and caused cell death. Tamoxifen itself induced autophagy in sensitive cells but not in resistant ones, and tamoxifen-resistant cells were sensitive to the induction of autophagy by other drugs. These results may point to an important role for autophagy in the sensitivity to tamoxifen.
