Endometrial profile of low-dose estradiol and tamoxifen combination therapy
Ontology highlight
ABSTRACT:
ORGANISM(S): Macaca fascicularis
SUBMITTER: Charles Wood
PROVIDER: E-GEOD-14518 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Combination therapy with estrogen and a selective estrogen receptor modulator (SERM) is a promising approach to safely alleviate important side effects related to estrogen deficiency in women at high risk for breast cancer. Data related to endometrial safety of estrogen+SERM co-therapies are limited, however. The primary goal of this study was to evaluate the endometrial profile of low-dose E2 and Tam alone and in combination.
2009-02-03 | GSE14518 | GEO
Project description:Here, we treated a nove ER-positive PDX (UCD12) supplemented with estrogen (E2) with or without thyroid hormone (TH) and/or tamoxifen (Tam). Each treatment cohort (E2 alone, E2 + TH, E2 + Tam, E2+ TH+Tam) tumor growth over time was monitored. Tumors treated with TH continued to grow more that E2 alone. Tamoxifen blocked E2-mediated tumor growth, however in the presence of TH this was not seen. This analysis identified thyroid hormone as a potential driver of tumor progression in the context of estrogen receptor positive PDX tumor model.
2020-05-14 | GSE131276 | GEO
Project description:Hight throughput techniques have revealed huge complexity in antisense RNAs in many organisms. We have explored the complexity of this class of transcripts and functional links to Polycomb silencing thought analysis of non-coding RNAs of Arabidopsis FLC. FLC is repressed and epigenetically silenced by prolonged cold, enabling plants to undergo the floral transition. Single nucleotide resolution tiling array revealed long non-coding transcripts covering the entire FLC locus. The most abundant of these are capped and polyadenylated, initiate over a 100 nucleotide window just downstream of the sense polyA site, are differentially spliced and terminate either within the sense gene or its promoter. Their levels correlate with FLC sense transcripts in all mutants and conditions tested except cold treatment. The antisense transcripts were strongly but transiently cold-induced, much earlier than other vernalization markers, and this coincided with reduction in sense FLC transcription but not sense FLC mRNA levels. Addition of the FLC antisense 5'/sense 3' region to a GFP transgene was sufficient to confer cold-induced silencing of thet fusion; however this silencing was not epigenetically manteined. These processes were all independent of the function of the Polycomb proteins required for maintenance of FLC silencing. Our data suggest that FLC antisense transcripts induce transient FLC transcriptional silencing, possibly through promoter interference, with the epigenetic silencing requiring subsequent recruitment of Polycomb machinery. Total seedling RNA from different genotypes and different conditions: WT, FRIGIDA, 35s::FCA (giving overexpression of FCA), FRIGIDA + 2 weeks cold, FRIGIDA + 2 weeks cold + 7 days warm.
2009-12-31 | E-GEOD-16977 | biostudies-arrayexpress
Project description:Menopausal estrogen (E2) replacement therapy increases the risk of estrogen receptor (ER)-positive epithelial ovarian cancers (EOC). Whether E2 is tumorigenic or promotes expansion of undiagnosed pre-existing disease is unknown. To determine E2 effects on tumor promotion, we developed an intraperitoneal mouse xenograft model using ZsGreen fluorescent ER- 2008 and ER+ PEO4 human EOC cells. Tumor growth was quantified by in vivo fluorescent imaging. In ER+ tumors, E2 significantly increased size, induced progesterone receptors, and promoted lymph node metastasis, confirming that ER are functional and foster aggressiveness. Laser captured human EOC cells from ER- and ER+ xenografted tumors were profiled for expression of E2-regulated genes. Three classes of E-regulated EOC genes were defined, but less than 10% were shared with E-regulated breast cancer genes. Since breast cancer selective ER modulators (SERM) are therapeutically ineffective in EOC, we suggest that our EOC-specific E-regulated genes can assist pharmacologic discovery of ovarian targeted SERM.
2011-05-13 | GSE22600 | GEO
Project description:There are concerns regarding possible reproductive toxicity from consumption of soy including an increased risk of endometriosis and endometrial cancer. We used global uterine gene expression profiles in adult ovariectomized (OVX) female rats assessed by RNAseq to examine the estrogenicity of soy protein isolate (SPI) and the potential for feeding SPI to alter estrogen signaling in the uterus. Rats were fed AIN93G diets made with casein (CAS) or SPI from postnatal day (PND) 30. Rats were OVX on PND 50 and infused with 17 beta-estradiol (E2) or vehicle. E2 increased uterine wet weight (P<0.05) and significantly altered expression of 2084 uterine genes. In contrast, SPI feeding had no effect on uterine weight and only altered expression of 177 genes. Overlap between E2 and SPI genes was limited to 69 genes (3%). GO analysis indicated significant differences in uterine biological processes affected by E2 and SPI and little evidence for recruitment of ER alpha to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were cancer pathways and extracellular organization. SPI feeding up-regulated uterine PPAR signaling and fatty acid metabolism. The combination of E2 and SPI feeding resulted in significant regulation of 715 fewer genes relative to E2 alone. In a separate experiment, the combination of E2 and SPI reversed the ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA). These data suggest SPI does not act as a weak estrogen in the uterus but appears to be a selective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and to be anti-estrogenic in the presence of endogenous estrogens. Rat uterus mRNA of ovariectomized adult female rats subject to four different diets (Caseine, Caseine + E2, Soy and Soy+E2 ) were sequenced, in triplicate, in an Illumina GAIIx sequencer.
2015-06-13 | E-GEOD-69819 | biostudies-arrayexpress
Project description:Menopausal estrogen (E2) replacement therapy increases the risk of estrogen receptor (ER)-positive epithelial ovarian cancers (EOC). Whether E2 is tumorigenic or promotes expansion of undiagnosed pre-existing disease is unknown. To determine E2 effects on tumor promotion, we developed an intraperitoneal mouse xenograft model using ZsGreen fluorescent ER- 2008 and ER+ PEO4 human EOC cells. Tumor growth was quantified by in vivo fluorescent imaging. In ER+ tumors, E2 significantly increased size, induced progesterone receptors, and promoted lymph node metastasis, confirming that ER are functional and foster aggressiveness. Laser captured human EOC cells from ER- and ER+ xenografted tumors were profiled for expression of E2-regulated genes. Three classes of E-regulated EOC genes were defined, but less than 10% were shared with E-regulated breast cancer genes. Since breast cancer selective ER modulators (SERM) are therapeutically ineffective in EOC, we suggest that our EOC-specific E-regulated genes can assist pharmacologic discovery of ovarian targeted SERM. 15 samples were included in this experiment with a 2x2 factorial design with 2 different cell lines (2008 and PEO4) and 2 different hormone treatments (E for Estrogen and C for Placebo Control) and 4 replicates per treatment. 1 sample was excluded (a replicate of PEO4 with C treatment) because of poor quality.
2011-05-13 | E-GEOD-22600 | biostudies-arrayexpress
Project description:Treatment with the breast cancer drug tamoxifen confers a risk of developing uterine tumors or other endometrial pathologies. Tamoxifen is a selective estrogen receptor modulator, which demonstrates tissue-specific activity although the mechanisms remain poorly understood. Both estradiol and tamoxifen act as estrogen agonists on the human uterus, and therefore have the potential to promote carcinogenicity. Estradiol and tamoxifen elicit cellular responses via the estrogen receptors (ER), which are involved in multiple signalling pathways. The effects at the molecular level are further influenced by the differential recruitment of co-factors and the presence of specific promoter motifs in target genes. In this study, ER positive (+) Ishikawa cells are used as a model to investigate the overall effect of treatment with either 17b-estradiol or 4-hydroxytamoxifen on the gene expression profiles. Ishikawa cells were serum-starved for 72 hours prior to treatment with 10-8M 17b-estradiol (E2) or 10-6M 4-hydroxytamoxifen (tam) for 24 or 48 hours. Cells were collected for total RNA extraction, and the quality and quantity of the RNA was determined spectrophotometrically. cDNA was prepared from treated (tam or E2) and control (vehicle only) Ishikawa cells, and was both forward and reverse labelled using Cy-3 dUTP/ Cy-5 dUTP and hybridised to oligo microarray slides representing >19,000 human genes (MRC HGMP-RFC). The data were analysed using GenePix Pro 3.0 software (Axon instruments) and statistical analyses applied to select significant gene changes (p<0.05).
2010-07-01 | E-GEOD-3762 | biostudies-arrayexpress
Project description:Virus infection and over expression of protein in cytosol induce a subset of HSP70s. We named this response the Cytosolic Protein Response (CPR) and have been investigating it in the context of a parallel mechanism in the soluble cytosol with the UPR, and as a subcomponent of the larger HS response. This experiment was carried out to study the transcriptional aspect of CPR. In this analysis, we have triggered CPR by infiltrating proline analogue, L-azetidine-2-carboxylic acid (AZC) into Arabidopsis mature leaves. Since AZC trigger unfolded protein response(UPR) in ER as well as CPR, we have included tunicamycin treatment, which is a specific inducer of UPR to subtract the effect of UPR from the AZC response. Heat shocked samples were included to identify CPR as a subcomponent of larger HS response. We used microarray data to identify the genes upregurated by CPR. These genes were commonly upregulated by AZC and HS but not by tunicamycin treatment. Experiment Overall Design: Arabidopsis mature leaves were infiltrated with AZC or L-Proline (control of AZC) and tunicamycin or DMF(solvent control of tunicamycin). For the heat shock treatment, six mature leaves were detached from plant and incubated at 37 °C or 20°C (as a control) for a period of 1h. The experiment was repeated three times for AZC and HS treatment (3 biological replication). Tunicamycin experiment was repeated five times due to large valiation in the responses (5 biological replication).
2009-01-13 | E-GEOD-11758 | biostudies-arrayexpress
Project description:To investigate molecular mechanisms of resistance, we used two different in vivo xenograft models of estrogen receptor-positive (ER+) breast cancer, with or without HER2 over-expression (MCF7/HER2-18 and MCF7 wt, respectively). Mice with established tumors were assigned to the following treatment groups: continued estrogen supplementation (E2), estrogen deprivation (ED), ED plus tamoxifen (Tam), all with or without the EGFR tyrosine kinase inhibitor gefinitinib (G). Another group received ED plus the antiestrogen fulvestrant (MCF7 wt only). Tumors with acquired or de novo resistance to these endocrine therapies were profiled for mRNA expression using Affymetrix Genechip arrays. Experiment Overall Design: MCF7 xenografts were established in ovariectomized five to six week-old nu/nu athymic nude mice supplemented with 0.25 mg 21 day release estrogen pellets by inoculating subcutaneously (s.c.) 5E-6 cells. When tumors reached the size of 150-200 mm3 (3-5 weeks), the animals were randomly allocated to continued estrogen (E2), continued estrogen with gefitinib (E2+G; 100mg/kg, 5 days/week), estrogen withdrawal alone (ED; by removal of the estrogen pellets), and estrogen withdrawal plus tamoxifen citrate (Tam; 500 microg/animal s.c. in peanut oil, 5 days/week), with either gefitinib (Tam+G; 100mg/kg, 5 days/week) or vehicle (1% Tween 80) administered via gavage, as well as estrogen withdrawal plus fulvestrant (ICI 182,780) in the MCF7 wt model (Fulv; 5mg/mouse s.c. once weekly), and estrogen withdrawal with gefitinib (ED+G). Tumors were harvested for molecular studies when they became resistant to treatment and reached the size of 1000 mm3 (n=7).
2009-01-13 | E-GEOD-8139 | biostudies-arrayexpress
Project description:To investigate molecular mechanisms of resistance, we used two different in vivo xenograft models of estrogen receptor-positive (ER+) breast cancer, with or without HER2 over-expression (MCF7/HER2-18 and MCF7 wt, respectively). Mice with established tumors were assigned to the following treatment groups: continued estrogen supplementation (E2), estrogen deprivation (ED), ED plus tamoxifen (Tam), all with or without the EGFR tyrosine kinase inhibitor gefinitinib (G). Another group received ED plus the antiestrogen fulvestrant (MCF7 wt only). Tumors with acquired or de novo resistance to these endocrine therapies were profiled for mRNA expression using Affymetrix Genechip arrays. Experiment Overall Design: MCF7 xenografts were established in ovariectomized five to six week-old nu/nu athymic nude mice supplemented with 0.25 mg 21 day release estrogen pellets by inoculating subcutaneously (s.c.) 5E-6 cells. When tumors reached the size of 150-200 mm3 (3-5 weeks), the animals were randomly allocated to continued estrogen (E2), continued estrogen with gefitinib (E2+G; 100mg/kg, 5 days/week), estrogen withdrawal alone (ED; by removal of the estrogen pellets), and estrogen withdrawal plus tamoxifen citrate (Tam; 500 microg/animal s.c. in peanut oil, 5 days/week), with either gefitinib (Tam+G; 100mg/kg, 5 days/week) or vehicle (1% Tween 80) administered via gavage, as well as estrogen withdrawal plus fulvestrant (ICI 182,780) in the MCF7 wt model (Fulv; 5mg/mouse s.c. once weekly), and estrogen withdrawal with gefitinib (ED+G). Tumors were harvested for molecular studies when they became resistant to treatment and reached the size of 1000 mm3 (n=7).
2009-01-13 | E-GEOD-8140 | biostudies-arrayexpress