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SRP044611
Homo sapiens
3 Downloadable Samples
IlluminaGenomeAnalyzerII
Description
A c-Src inhibitor blocks estrogen (E2)-induced stress and converts E2 responses from inducing apoptosis to growth stimulation in E2-deprived breast cancer cells. A reprogrammed cell line, MCF-7:PF, results with features of functional estrogen receptor (ER) and over-expression of insulin-like growth factor-1 receptor beta (IGF-1Rß). We addressed the question of whether the selective ER modulator 4-hydroxytamoxifen (4-OHT) could target ER to prevent E2-stimulated growth in MCF-7:PF cells. Selected expression of mRNA was measured through real-time RT-PCR. Global gene expression was analyzed by microarray and RNA-seq analysis. Unexpectedly, both 4-OHT and E2 stimulated cell growth in a concentration-dependent manner. Global gene expression analysis showed a remarkable overlap in genes regulated in the same direction by E2 and 4-OHT. Pathway enrichment analysis of the 280 genes commonly deregulated by 4-OHT and E2 revealed functions mainly related to membrane, cytoplasm, and metabolic processes. Further analysis of 98 up-regulated genes by both 4-OHT and E2 uncovered a significant enrichment in genes associated with membrane remodeling, cytoskeleton reorganization, cytoplasmic adapter proteins, cytoplasm organelles proteins, and related processes. 4-OHT was more potent than E2 to up-regulate some membrane remodeling molecules, such as EHD2, FHL2, HOMER3 and RHOF. In contrast, 4-OHT acted as an antagonist to inhibit expression of the majority of enriched membrane-associated genes in wild-type MCF-7 cells. Long-term selection pressure has changed the cell population responses to 4-OHT. Membrane-associated signaling is critical for 4-OHT-stimulated cell growth in MCF-7:PF cells. This study provides a rationale for the further investigation of targeted therapy for tamoxifen resistant patients. Overall design: Wild-type MCF-7 cells were treated with vehicle control (0.1% ethanol), E2 (10-9 mol/L) and 4-OHT (10-6 mol/L) respectively for 24 hours.
Publication Title
Identification of gene regulation patterns underlying both oestrogen- and tamoxifen-stimulated cell growth through global gene expression profiling in breast cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 36 Downloadable Samples
- Illumina HiSeq 2000
Description
Alzheimer's disease is a devastating neurodegenerative disease eventually leading to dementia. An effective treatment does not yet exist. Here we show that oral application of the compound anle138b restores hippocampal synaptic and transcriptional plasticity as well as spatial memory in a mouse model for Alzheimer's disease, when given orally before or after the onset of pathology. At the mechanistic level we provide evidence that anle138b blocks the formation of conducting Aß pores without changing the membrane embedded Aß-oligomer structure. In conclusion, our data suggest that anle138b is a novel and promising compound to treat AD-related pathology that should be investigated further. Overall design: APPdelta9 and Wildtype mouse treated with anle138b or placebo
Publication Title
The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology.
Sample Metadata Fields
Age, Cell line, Subject
View Samples- Rattus norvegicus
- 11 Downloadable Samples
- Illumina HiSeq 2500
Description
Comparison of gene expression level by Illumina sequencing of rat skin from young and old animals. We identified differentially expressed genes and provide functional profiles, which give insights into the aging process of short-lived rodents. Overall design: 9 skin samples, 4-5 animals per group, 2 groups: 1) young males, 2) old males
Publication Title
Tissue-, sex-, and age-specific DNA methylation of rat glucocorticoid receptor gene promoter and insulin-like growth factor 2 imprinting control region.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
Comparison of gene expression level by Illumina sequencing of rat liver from young and old animals. We identified differentially expressed genes and provide functional profiles, which give insights into the aging process of short-lived rodents. Overall design: 9 liver samples, 4-5 animals per group, 2 groups: 1) young males, 2) old males
Publication Title
Tissue-, sex-, and age-specific DNA methylation of rat glucocorticoid receptor gene promoter and insulin-like growth factor 2 imprinting control region.
Sample Metadata Fields
No sample metadata fields
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