Intermittent treatment on exemestane acquired resistance
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE149406 | GEO | 2020/12/31
REPOSITORIES: GEO
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Project description:MCF-7aro cells were used to generate a cell culture model system that is resistant to 3 aromatase inhibitors (AIs), letrozole, anastrozole and exemestane. For comparison, the MCF-7aro cells were also used to generate the tamoxifen-resistant cells as well as long-term estrogen deprived, LTEDaro. Affymetrix microarray analysis was performed to determine changes in gene expression that are unique to AI-resistance. Experiment Overall Design: For control purposes, MCF-7aro cells were cultured without any hormone or inhibitor as well as a hormone-only control (T-only). Resistant cells were grown in the presence of testosterone, T+LET R (letrozole), T+ANA R (anastrozole), T+EXE R (exemestane), T+TAM R (Tamoxifen). In addition, testosterone-free resistant lines were generated, LTEDaro, ANA R and EXE R. 6 replicates were generated for the hormone-containing resistant lines and 3 replicates for the hormone-free resistant lines.
2008-04-04 | E-GEOD-10911 | biostudies-arrayexpress
Project description:The role of estrogen and testosterone in the regulation of gene expression in the proximal reproductive tract is not completely understood. To address this question, mice were treated with testosterone or estradiol and RNA from the efferent ducts and caput epididymis was processed and hybridized to Affymetrix MOE 430 2.0 microarrays. Analysis of array output identified probe sets in each tissue with altered levels in hormone treated versus control animals. Hormone treatment efficacy was confirmed by determination of serum hormone levels pre- and post-treatment and observed changes in transcript levels of previously reported hormone-responsive genes. Tissue-specific hormone sensitivity was observed with 2867 and 3197 probe sets changing significantly in the efferent ducts after estrogen and testosterone treatment, respectively. In the caput epididymis, 117 and 268 probe sets changed after estrogen and testosterone treatment, respectively, demonstrating a greater response to hormone in the efferent ducts than the caput epididymis. Transcripts sharing similar profiles in the intact and hormone-treated animals compared with castrated controls were also identified. Ontological analysis of probe sets revealed a significant number of hormone-regulated transcripts encode proteins associated with lipid metabolism, transcription and steroid metabolism in both tissues. Real-time RT-PCR was employed to confirm array data and investigate other potential hormone-responsive regulators of proximal reproductive tract function. The results of this work reveal previously unknown responses to estrogen in the caput epididymis and to testosterone in the efferent ducts as well as tissue specific hormone sensitivity in the proximal reproductive tract.
2009-12-31 | GSE17553 | GEO
Project description:The role of estrogen and testosterone in the regulation of gene expression in the proximal reproductive tract is not completely understood. To address this question, mice were treated with testosterone or estradiol and RNA from the efferent ducts and caput epididymis was processed and hybridized to Affymetrix MOE 430 2.0 microarrays. Analysis of array output identified probe sets in each tissue with altered levels in hormone treated versus control animals. Hormone treatment efficacy was confirmed by determination of serum hormone levels pre- and post-treatment and observed changes in transcript levels of previously reported hormone-responsive genes. Tissue-specific hormone sensitivity was observed with 2867 and 3197 probe sets changing significantly in the efferent ducts after estrogen and testosterone treatment, respectively. In the caput epididymis, 117 and 268 probe sets changed after estrogen and testosterone treatment, respectively, demonstrating a greater response to hormone in the efferent ducts than the caput epididymis. Transcripts sharing similar profiles in the intact and hormone-treated animals compared with castrated controls were also identified. Ontological analysis of probe sets revealed a significant number of hormone-regulated transcripts encode proteins associated with lipid metabolism, transcription and steroid metabolism in both tissues. Real-time RT-PCR was employed to confirm array data and investigate other potential hormone-responsive regulators of proximal reproductive tract function. The results of this work reveal previously unknown responses to estrogen in the caput epididymis and to testosterone in the efferent ducts as well as tissue specific hormone sensitivity in the proximal reproductive tract. Adult animals were castrated or sham-castrated, allowed to recover for 14 days, and then treated with 0.015 mg estradiol (castrated), 0.015 mg testosterone propionate (castrated), or vehicle (castrated and sham-castrated as biological controls) in duplicate. Efferent duct and caput epididymis was collected from each sample and analyzed. Duplicates are included in the provided data and numbered 1 or 2 for each treatment regimen.
2009-12-30 | E-GEOD-17553 | biostudies-arrayexpress
Project description:Androgenic steroids are increasingly used for hormone therapy of postmenopausal women and abused as life style drugs and for doping purposes, though knowledge about associated health risks in females is very limited. In order to understand more about short- and long-term androgen effects on a molecular level, we have analyzed hepatic gene expression in female C57BL/6 mice immediately after subcutaneous treatment with testosterone for 3 weeks and after 12 weeks hormone withdrawal using Affymetrix array technology and quantitative real-time RT-PCR. Among about 14,000 genes examined, 48 were up- and 65 genes were downregulated by testosterone after 3-weeks treatment and about 50% of these changes persisted even 12 weeks after testostrone withdrawal. In addition to obvious risks such as induction of hepatocellular carcinomas and virilization of liver metabolism, testosterone induced a series of changes, as e.g. dysregulation of hepatic gene expression due to incomplete conversion of female to male phenotype â in particular downregulation of cytochrom P450 isoforms and sulfotransferases. As a long-term testosterone effect, transcripts emerged in the liver that are normally specific for the exocine pancreas including amylase 2, ribonuclease 1, and several trypsin-, chymotrypsin-, and elastase-like proteases. This transdifferentiation of hepatic to exocrine pancreatic tissue indicates that testosterone can initiate long-lasting differentiation programs, which â once induced â progress even after androgen withdrawal. This may have far-reaching consequences difficult to foresee implying long-term hazards of testosterone-treatment for female health that have not been taken into account yet. Mice were treated with testosterone or sesame oil (vehicle) for three weeks twice a week. Gene expression in the liver was analyzed either directly after treatment or after three weeks of hormone/vehicle withdrawal. For each of these four groups, three individual mice were used as biological replicates.
2010-03-03 | E-GEOD-13388 | biostudies-arrayexpress
Project description:We analyzed androgens effects on human neural stem cells (hNSCs) by RNA-sequencing after either DMSO (solvent), DHT 100nM, 10nM, Testosterone 100nM, 10nM, R1881 1nM or retinoic acid 1µM 24 hours treatment in order to find the role of androgen receptor (AR) during brain development.
2018-02-01 | GSE86457 | GEO
Project description:One key reason for T cell exhaustion is continuous antigen exposure. Early exhausted T cells can reverse exhaustion and differentiate into fully functional memory T cells if removed from persisting antigen stimulation. Therefore, this study viewed T cell exhaustion as an over-activation status induced by chronic antigen stimuli. This study hypothesized that blocking TCR signal intermittently to terminate over-activation signal can defer the developmental process of T cell exhaustion. In this study, B16F10 melanoma-bearing mice were treated with tacrolimus (FK506) every five days. The tumor size and tumor-infiltrating lymphocytes (TILs) were analyzed. We found that intermittent administration of tacrolimus significantly inhibited tumor growth, and this effect was mediated by CD8+T cells. Intermittent tacrolimus treatment facilitated the infiltration of CD8+TILs. RNA-seq and quantitative RT-PCR of sorted CD8+TILs showed the expression of Nr4a1 (an exhaustion-related transcription factor) and Ctla4 (a T cell inhibitory receptor) was remarkably downregulated. These results indicated that intermittently blocking TCR signal by tacrolimus can promote anti-tumor immunity and inhibit the tumor growth in melanoma-bearing mice, inhibiting the transcription of several exhaustion-related genes, such as Nr4a1 and Ctla4.
2022-02-03 | GSE190872 | GEO
Project description:Analysis of hormone effects on irradiated LBNF1 rat testes, which contain only somatic cells except for a few type A spermatgogonia. Rats were treated for 2 weeks with either sham treatment (group X), hormonal ablation (GnRH antagonist and the androgen receptor antagonist flutamide, group XAF), testosterone supplementation (GnRH antagonist and testosterone, group XAT), and FSH supplementation ((GnRH antagonist, androgen receptor antagonist, and FSH, group XAFF). Results provide insight into identifying genes in the somatic testis cells regulated by testosterone, LH, or FSH.
2009-09-30 | GSE15243 | GEO
Project description:Goal of the experiment: To examine the effects of estrogen and testosterone on gene expression in the rat mesenteric arteries. Brief description of the experiment: A dramatic difference exists in the timing of development of cardiovascular disease in men vs. women. The primary candidates underlying the cause of gender differences in cardiovascular disease are the sex steroids, estrogen and testosterone. The effect of estrogen on the cardiovascular system has been expected to be protective but this concept has become controversial. The effect of testosterone on the cardiovascular system is considered to be deleterious. In spite of these concepts there is little data on the direct effects of estrogen and testosterone on gene expression in the vasculature. Since estrogen and testosterone exert many of their effects through genomic mechanisms, the DNA microarray is an excellent tool for assessing their effects in the vasculature. In this study, ovariectomized Sprague Dawley rats were treated for 4 days with vehicle (sesame oil), estradiol benzoate (0.15 mg/kg/day), or testosterone (1 mg/kg/day). The mesenteric arteries were obtained, total RNA was extracted, and CodeLink Uniset Rat I DNA microarrays (GE) were used to identify differential gene expression. Seven genes were identified as differentially expressed from the DNA microarray data and confirmed by real time RT-PCR. The expression of D site albumin promoter binding protein and fatty acid synthase were increased in response to both estrogen and testosterone. 3alpha-hydroxysteroid dehydrogenase, interleukin 4 receptor, JunB and c-Fos expression were increased by estrogen but not by testosterone. The aryl hydrocarbon nuclear translocator-like was reduced by testosterone. These data identify genes not previously known to be responsive to estrogen and testosterone in the vasculature. Keywords: hormone treatment, vasculature, gender differences Experimental factors: hormone treatment Keywords: hormone treatment
2007-09-30 | GSE4782 | GEO
Project description:Analysis of hormone effects on irradiated LBNF1 rat testes, which contain only somatic cells except for a few type A spermatgogonia. Rats were treated for 2 weeks with either sham treatment (group X), hormonal ablation (GnRH antagonist and the androgen receptor antagonist flutamide, group XAF), testosterone supplementation (GnRH antagonist and testosterone, group XAT), and FSH supplementation ((GnRH antagonist, androgen receptor antagonist, and FSH, group XAFF). Results provide insight into identifying genes in the somatic testis cells regulated by testosterone, LH, or FSH. Experiment Overall Design: 14 Sample replicates of sham treatment, 11 Sample replicates of hormonal ablation, 5 Sample replicates of testosterone supplementation, and 5 Sample replicates of FSH supplementation were studied.
2009-10-10 | E-GEOD-15243 | biostudies-arrayexpress
Project description:Wild type (wt) MCF7 cells, modelling breast cancer at primary diagnosis, were cultured in phenol red-free RPMI supplemented with 10% FBS and 1nM estradiol (E2). Long-term oestrogen deprived (LTED) cell lines, which model resistance to endocrine therapy, were cultured in phenol red-free RPMI in the absence of exogenous E2 and supplemented with 10% dextran charcoal-stripped bovine serum (DCC). Samples were harvested at baseline and at the point of resistance (LTED). To reveal differential protein abundances between wt-MCF7 and MCF7 LTED, the peptides were labelled with chemical labelling and underwent fractionation using OFFGEL electrophoresis.
2016-06-01 | PXD004085 | Pride