Crosstalk between Aryl hydrocarbonreceptor (AHR) and Estrogen receptor (ER) is poorly understood, but seems to play a major role in female reproductive organs.
Cross-Talk in the Female Rat Mammary Gland: Influence of Aryl Hydrocarbon Receptor on Estrogen Receptor Signaling.
Sex, Specimen part
View SamplesGlucocorticoids (GC) are pivotal in the treatment of childhood acute lymphoblastic leukaemia (ALL) but resistance is a continuing clinical problem with the underlying mechanisms still unclear. An isobaric tag proteomic approach was used to compare protein profiles of the B lineage ALL GC-sensitive cell line, PreB 697, and its GC-resistant sub-line, R3F9, before and after dexamethasone exposure. Two transcription factors involved in B- cell differentiation, PAX5 and IRF4, were differentially regulated in the PreB 697 compared to the R3F9 cell line in response to GC. PAX5 basal protein expression was less in R3F9 compared to its GC-sensitive parent and was confirmed to be lower in other GC-resistant sub-lines of Pre B697 and was associated with a decreased expression of the PAX5 transcriptional target, CD19. Gene set enrichment analysis of microarray data from the cell lines showed that increasing GC-resistance was associated with differentiation from preB-II to an immature B-lymphocytes stage. GC resistant sub lines were shown to have a higher levels of p-JNK compared to the parent line and JNK inhibition caused re-sensitisation to GC. Reduced CD19 levels accompanying GC resistance was also apparent in some clinical samples, with high levels of MRD persisting after GC containing induction chemotherapy. Thus, quantitative proteomic analysis reveals a role for PAX5 and maturation as a recurrent mechanism underlying glucocorticoid resistance in ALL and identifies JNK inhibitors as a possible re-sensitising therapy.
Quantitative proteomic analysis reveals maturation as a mechanism underlying glucocorticoid resistance in B lineage ALL and re-sensitization by JNK inhibition.
No sample metadata fields
View SamplesExamination of crosstalk between Aryl hydrocarbonreceptor (AHR) and Estrogen receptor (ER) in the rat uterus on the level of mRNA transcriptome
Effects of the aryl hydrocarbon receptor agonist 3-methylcholanthrene on the 17β-estradiol regulated mRNA transcriptome of the rat uterus.
Sex, Specimen part, Treatment
View SamplesILLUMINATE (Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events), the phase 3 morbidity and mortality trial of torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, identified previously undescribed changes in plasma levels of potassium, sodium, bicarbonate, and aldosterone. A key question after this trial is whether the failure of torcetrapib was a result of CETP inhibition or of some other pharmacology of the molecule. The direct effects of torcetrapib and related molecules on adrenal steroid production were assessed in cell culture using the H295R as well as the newly developed HAC15 human adrenal carcinoma cell lines. Torcetrapib induced the synthesis of both aldosterone and cortisol in these two in vitro cell systems. Analysis of steroidogenic gene expression indicated that torcetrapib significantly induced the expression of CYP11B2 and CYP11B1, two enzymes in the last step of aldosterone and cortisol biosynthesis pathway, respectively. Transcription profiling indicated that torcetrapib and angiotensin II share overlapping pathways in regulating adrenal steroid biosynthesis. Hormone-induced steroid production is mainly mediated by two messengers, calcium and cAMP. An increase of intracellular calcium was observed after torcetrapib treatment, whereas cAMP was unchanged. Consistent with intracellular calcium being the key mediator of torcetrapibs effect in adrenal cells, calcium channel blockers completely blocked torcetrapib-induced corticoid release and calcium increase. A series of compounds structurally related to torcetrapib as well as structurally distinct compounds were profiled. The results indicate that the pressor and adrenal effects observed with torcetrapib and related molecules are independent of CETP inhibition.
Torcetrapib induces aldosterone and cortisol production by an intracellular calcium-mediated mechanism independently of cholesteryl ester transfer protein inhibition.
Specimen part, Cell line, Time
View SamplesHead and neck cancer is a hetergeneous disease. Based on previoulsy defined molecular subtypes we associated gene expression with response to different compounds. We used microarry gene expression for molecular subtyping
Basal subtype is predictive for response to cetuximab treatment in patient-derived xenografts of squamous cell head and neck cancer.
No sample metadata fields
View SamplesA transcription factor Nkx2-1 (also known as TTF-1) regulates the expression of different sets of genes. Gene expression analysis was performed using mRNAs from Nkx2-1-induced A549 cells compared to that from the control A549 cells. We used microarrays to detail the global program of gene expression controlled by Nkx2-1 and identified distinct classes of up-regulated and down-regulated genes.
Kras(G12D) and Nkx2-1 haploinsufficiency induce mucinous adenocarcinoma of the lung.
Cell line
View SamplesTransgenic mice (Scgb1a1-rtTA/[tetO]-KRAS.G12D/Nkx2-1+/-) develop mucinous lung tumors. Gene expression analysis was performed using mRNAs from the whole lungs of the mice compared to that of the control mice.
Kras(G12D) and Nkx2-1 haploinsufficiency induce mucinous adenocarcinoma of the lung.
Specimen part
View SamplesA comparison of gene expression in the mammary gland of lactating mice at day 9 after parturition between Akt -/- and wildtype individuals.
Isoform-specific requirement for Akt1 in the developmental regulation of cellular metabolism during lactation.
Sex, Age, Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Enhancing dopaminergic signaling and histone acetylation promotes long-term rescue of deficient fear extinction.
Sex, Specimen part
View SamplesBackground: Extinction-based exposure therapy is used in treating anxiety- and trauma-related disorders, however there is the need to improve its limited efficacy in individuals with impaired fear extinction learning and to facilitate the inadequate protection against return-of-fear phenomena.
Enhancing dopaminergic signaling and histone acetylation promotes long-term rescue of deficient fear extinction.
Sex, Specimen part
View Samples