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GSE45643
Homo sapiens
12 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Progesterone and estrogen are important drivers of breast cancer proliferation. Herein, we probed estrogen receptor- (ER) and progesterone receptor (PR) cross-talk in breast cancer models. Stable expression of PR-B in PR-low/ER+ MCF7 cells increased cellular sensitivity to estradiol and insulin-like growth factor 1 (IGF1), as measured in growth assays performed in the absence of exogenous progestin; similar results were obtained in PR-null/ER+ T47D cells stably expressing PR-B. Genome-wide microarray analyses revealed that unliganded PR-B induced robust expression of a subset of estradiol-responsive ER target genes, including cathepsin-D (CTSD). Estradiol-treated MCF7 cells stably expressing PR-B exhibited enhanced ER Ser167 phosphorylation and recruitment of ER, PR and the proline-, glutamate- and leucine-rich protein 1 (PELP1) to an estrogen response element in the CTSD distal promoter; this complex co-immunoprecipitated with IGF1 receptor (IGFR1) in whole-cell lysates. Importantly, ER/PR/PELP1 complexes were also detected in human breast cancer samples. Inhibition of IGF1R or phosphoinositide 3-kinase blocked PR-B-dependent CTSD mRNA upregulation in response to estradiol. Similarly, inhibition of IGF1R or PR significantly reduced ER recruitment to the CTSD promoter. Stable knockdown of endogenous PR or onapristone treatment of multiple unmodified breast cancer cell lines blocked estradiol-mediated CTSD induction, inhibited growth in soft agar and partially restored tamoxifen sensitivity of resistant cells. Further, combination treatment of breast cancer cells with both onapristone and IGF1R tyrosine kinase inhibitor AEW541 was more effective than either agent alone. In summary, unliganded PR-B enhanced proliferative responses to estradiol and IGF1 via scaffolding of ER-/PELP1/IGF1R-containing complexes. Our data provide a strong rationale for targeting PR in combination with ER and IGF1R in patients with luminal breast cancer.
Publication Title
Progesterone receptor-B enhances estrogen responsiveness of breast cancer cells via scaffolding PELP1- and estrogen receptor-containing transcription complexes.
Sample Metadata Fields
Treatment, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
BAF57, a component of the SWI/SNF chromatin remodeling complex conglomerate,modulates androgen receptor activity to promote prostate cancer. However the molecular consequences of tumor associated BAF57 elevation have remianed undefined in advanced disease such as castration resistant prostate cancer and/or metastasis
Publication Title
Aberrant BAF57 signaling facilitates prometastatic phenotypes.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
Illumina HiSeq 2500
Description
Gene expression analysis of T-cell acute lymphoblastic leukemia blast cells from either control mice or Dnmt3a knockout mice carrying a Notch1 Intracellular Domain (NICD) retrovirus Overall design: Comparison of gene expression between control and Dnmt3a-KO NICD-driven T-ALL
Publication Title
Dnmt3a regulates T-cell development and suppresses T-ALL transformation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
To study the molecular mediators of naturally rewarding effects of palatable food we used a model of palatable snacking (Ulrich-Lai et al., 2007) in which rats are given chronic, brief access to a limited amount of sucrose solution (30%). Single housed, male Long-Evans rats (250g) (n=12 per group) from Harlan Labs (Indianapolis, IN) received normal rat chow (Harlan Teklad) and water ad libitum for the duration of the experiment. After a one-week period of acclimation, rats were randomly assigned to drink treatment groups of either 30% sucrose solution or water. Rats received a 14-day regimen of twice daily (9:30 and 15:30) brief (maximum of 30 minutes) limited (up to 4 mL) access of their assigned drink solution. Drink solutions were delivered via a graduated sipper placed onto the cage top in addition to the existing water bottle and sippers were immediately removed when the animal had consumed 4mL or after the 30-minute access period, whichever occurred first. Drink intake, food intake, and body weight were monitored throughout the experiment to verify that the rats learned to drink sucrose, that they adjusted chow intake for calories consumed from sucrose (~10%), and that there was no effect on body weight gain as is normally seen with this model (Ulrich-Lai et al., 2007). Drink treatment terminated on day 14 and at 8:00 on the morning of day 15, the rats were sacrificed by rapid decapitation. BLA tissue was dissected, RNA extracted, and gene expression changes between water and sucrose groups were accessed by microarray.
Publication Title
Pleasurable behaviors reduce stress via brain reward pathways.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 159 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
We investigated the molecular mechanisms of chronic alcohol consumption or lipopolysaccharide insult by gene expression profiling in prefrontal cortex and liver of C57BL/6J mice.
Publication Title
Gene expression in brain and liver produced by three different regimens of alcohol consumption in mice: comparison with immune activation.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Production of functional proteins requires multiple steps including gene transcription and post-translational processing. MicroRNAs (miRNA) can regulate individual stages of these processes. Despite the importance of the cystic fibrosis transmembrane conductance regulator (CFTR) channel for epithelial anion transport, how its expression is regulated remains uncertain. We discovered that microRNA-138 regulates CFTR expression through its interactions with the transcriptional regulatory protein SIN3A. Treating airway epithelia with a miR-138 mimic increased CFTR mRNA and also enhanced CFTR abundance and transepithelial Cl- permeability independently of elevated mRNA levels. A miR-138 anti-miR had the opposite effects. Importantly, miR-138 altered the expression of many genes encoding proteins that associate with CFTR and may influence its biosynthesis. The most common CFTR mutation, F508, causes protein misfolding, degradation, and cystic fibrosis. Remarkably, manipulating the miR-138 regulatory network also improved biosynthesis of CFTR-F508 and restored Cl- transport to cystic fibrosis airway epithelia. This novel miRNA-regulated network directs gene expression from the chromosome to the cell membrane, indicating that an individual miRNA can control a cellular process broader than previously recognized. This discovery also provides new therapeutic avenues for restoring CFTR function to cells affected by the most common cystic fibrosis mutation.
Publication Title
A microRNA network regulates expression and biosynthesis of wild-type and DeltaF508 mutant cystic fibrosis transmembrane conductance regulator.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Sus scrofa
- 121 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A high protein diet during pregnancy affects hepatic gene expression of energy sensing pathways along ontogenesis in a porcine model.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 67 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptional response of skeletal muscle to a low-protein gestation diet in porcine offspring accumulates in growth- and cell cycle-regulating pathways.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 62 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
German landrace gilts were fed a high protein diet (HP, 30% CP) throughout their whole pregnancy. Subsequently hepatic transcriptome profiles of the offspring were analysed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn)
Publication Title
A high protein diet during pregnancy affects hepatic gene expression of energy sensing pathways along ontogenesis in a porcine model.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 59 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
German landrace gilts were fed an adequate protein diet (AP, 12% CP) throughout their whole pregnancy. Subsequently hepatic transcriptome profiles of the offspring were analysed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn).
Publication Title
A high protein diet during pregnancy affects hepatic gene expression of energy sensing pathways along ontogenesis in a porcine model.
Sample Metadata Fields
Specimen part
View Samples