Browse
Submit Data
Databases
API
Help

Dataset Information

6 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Altered Expression of ESR1, ESR2, PELP1 and c-SRC Genes Is Associated with Ovarian Cancer Manifestation.

ABSTRACT: Ovarian cancer remains the leading cause of death due to gynecologic malignancy. Estrogen-related pathways genes, such as estrogen receptors (ESR1 and ESR2) and their coregulators, proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), and proto-oncogene tyrosine-protein kinase c-Src (SRC) are involved in ovarian cancer induction and development, still they require in-depth study. In our study, tissue samples were obtained from 52 females of Caucasian descent (control group without cancerous evidence (n = 27), including noncancerous benign changes (n = 15), and the ovarian carcinoma (n = 25)). Using quantitative analyses, we investigated ESRs, PELP1, and SRC mRNA expression association with ovarian tumorigenesis. Proteins' presence and their location were determined by Western blot and immunohistochemistry. Results showed that PELP1 and SRC expression levels were found to differ in tissues of different sample types. The expression patterns were complex and differed in the case of ovarian cancer patients compared to controls. The most robust protein immunoreactivity was observed for PELP1 and the weakest for ESR1. The expression patterns of analyzed genes represent a potentially interesting target in ovarian cancer biology, especially PELP1. This study suggests that specific estrogen-mediated functions in the ovary and ovary-derived cancer might result from different local interactions of estrogen with their receptors and coregulators.

SUBMITTER: Englert-Golon M

PROVIDER: S-EPMC8228770 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

ESR1 and ESR2 gene polymorphisms are associated with human reproduction outcomes in Brazilian women.

Project description:BackgroundImportant candidate genes involved in the ovarian response to exogenous FSH are the estrogen receptor genes (ESRs), since the effects of estrogens on follicle growth, maturation and oocyte release. It is known that some markers of ovarian stimulation can help to personalize the treatment, adjusting the dose of exogenous rFSH, thus preventing excessive wear of the patient. Inspired on this information we aimed to analyze four different polymorphisms in the estrogen receptor genes ESR1: rs2234693/T-397C (PvuII) and rs9340799/A-351G (Xbal) and ESR2: rs4986938/G1082A (RsaI) and rs1256049/A + 1730G (AluI), and their association with assisted reproduction outcomes in Brazilian women that underwent in vitro fertilization (IVF).MethodsA cross-sectional study was performed involving 136 infertile women less than 39 years of age with normal ovarian reserve. Patients were divided according to the same COH protocol for statistical analysis. The Taqman assay was used for PvuII and XbaI of ESR1, and RsaI and AluI of ESR2 genotyping. Serum estradiol and FSH were measured by Elisa assay.ResultsThe PvuII (ESR1) TT and RsaI (ESR2) GG genotypes were associated with a longer induction period and higher doses of medication (p < 0.03). The XbaI (ESR1) AA genotype was associated with better COH results, including a larger number of follicles, mature oocytes, embryos, and good quality embryos (p < 0.05). The AluI GG genotype showed an association with the Ovarian Hyperstimulation Syndrome (OHSS) (p = 0.03). According to the haplotype analysis of ER1 (PvuII/XbaI), we demonstrated that the CA combination increases by 0.68 the number of good quality embryos while the TG decreases it by 0.71 (p = 0.04).ConclusionER polymorphisms have an association with the assisted reproduction outcomes in Brazilian women.

| S-EPMC4302593 | biostudies-literature

Inherited variations in AR, ESR1, and ESR2 genes are not associated with prostate cancer aggressiveness or with efficacy of androgen deprivation therapy.

Project description:Sex steroid hormone receptors mediate essential processes in normal prostate growth and contribute to prostate cancer development.In this study, we investigated the association between common inherited variation of the AR, ESR1, and ESR2 genes and two clinically relevant traits: the risk of developing aggressive prostate cancer and the response to androgen deprivation therapy (ADT) in a hospital-based cohort. A total of 43 tagging single nucleotide polymorphisms covering the loci of AR (n = 4), ESR1 (n = 32), and ESR2 (n = 7) were successfully genotyped in 4,073 prostate cancer cases.None of these single nucleotide polymorphisms were significantly associated with disease aggressiveness as assessed by the D'Amico risk classification, pathologic stage, or the response to ADT.Our results suggest that common genetic variations in AR, ESR1, or ESR2 are not strongly associated with prostate cancer aggressiveness or response to ADT.Our study did not find convincing evidence of inherited variations in the major receptors for androgens and estrogens and their associations with prostate cancer traits.

| S-EPMC3755451 | biostudies-literature

Association with litter size of new polymorphisms on ESR1 and ESR2 genes in a Chinese-European pig line.

Project description:The objective of this study was to search for polymorphisms in the coding region of the estrogen receptors 1 and 2 (ESR1 and ESR2) and to analyze the effects of these variants and the well known intronic ESR1 PvuII polymorphism on litter size in a Chinese-European pig line. We identified five silent single nucleotide polymorphisms (SNP) in the ESR1 cDNA: c.669T > C (exon 3), c.1227C > T (exon 5), c.1452C > T (exon 7), c.1665T > C and c.1755A > G (exon 8). One pair of these SNP (c.1665T > C and c.1755A > G) co-segregated in the analyzed line, and the SNP c.669T > C showed the same segregation pattern as the PvuII polymorphism. These polymorphisms were tested in this study, although the c.1452C > T SNP within exon 7 was not analyzed due to its low informativeness. In the ESR2 cDNA, one missense SNP was found within exon 5, which caused an amino acid substitution in the coded protein: "c.949G > A (p.Val317Met)" and was tested on sow litter size. Information on 1622 litter records from 408 genotyped sows was analyzed to determine whether these SNP influenced the total number of piglets born (TNB) or the number of born alive (NBA). The polymorphisms ESR1: [ PvuII; c.669T > C] , ESR1: [ c.1665T > C; c.1755A > G] and ESR2: c.949G > A showed no statistically significant association with litter size. However, the ESR1: c.1227T allele was significantly associated with TNB. The additive substitution effect was estimated to be 0.40 piglets born per litter (P < 0.03), and no dominance effects were observed. This SNP could be useful in assisted selection for litter size in some pig lines, as a new genetic marker in linkage disequilibrium with the causative mutation.

| S-EPMC2682837 | biostudies-other

ESR1 and ESR2 genotypes and the age at menarche in idiopathic scoliosis

Project description: Not available

| S-EPMC4290577 | biostudies-literature

Expression of ESR1 and ESR2 oestrogen receptor encoding gene and personality traits - preliminary study.

Project description:IntroductionThe main objective of the study is to examine the hypothesis claiming a correlation between personality traits measured with the use of the Minnesota Multiphasic Personality Inventory (MMPI-2) personality questionnaire and the expression of the ERα (ESR1) and ERβ (ESR2) encoding gene in patients suffering from depression.Material and methodsThe experiment was carried out on a group of 44 individuals with depression. The Polish variant of the MMPI-2 was applied with the aim of assessing personality traits. Furthermore, the authors evaluated the expression of the genes encoding the oestrogen receptors (ERα and ERβ) at the mRNA level and protein level in the studied population.ResultsNo significant differences in the expression of ERα and ERβ encoding genes were found and confirmed in the patients with the first episode of depression and those suffering from subsequent episodes of the disease. No differences were found between women and men, either. In women a positive relationship was found between the scale of psychopathy (p = 0.04), paranoia (p = 0.01), and mania (p = 0.03) and expression for the ERα encoding gene at the mRNA level. A negative relationship was found between the mania scale and ERβ encoding gene expression at mRNA (p = 0.03) and protein (p = 0.04) levels. In males a positive relationship between anxiety as a personality trait and expression of the ERβ receptor encoding gene at mRNA level (p = 0.03) and protein level (p = 0.03) was found.ConclusionsPersonality traits may be linked with the expression of genes encoding oestrogen receptors (ERα and ERβ) among patients with depressive disorders.

| S-EPMC6970415 | biostudies-literature

Elevated seminal plasma estradiol and epigenetic inactivation of ESR1 and ESR2 is associated with CP/CPPS.

Project description:Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is associated with urinary tract symptoms and hormonal imbalances amongst others. The heterogeneous clinical presentation, unexplored molecular background and lack of prostate biopsies complicate therapy. Here, using liquid biopsies, we performed a comprehensive translational study on men diagnosed with CP/CPPS type III (n= 50; median age 39.8, range 23-65) and age-matched controls (n= 61; median age 36.8, range 20-69), considering biochemical parameters of blood and ejaculates, and epigenetic regulation of the estrogen receptor genes (ESR1 and ESR2) in leukocytes isolated from blood (systemic regulation) and in somatic cells isolated from ejaculates (local regulation). We found elevated 17β-estradiol (E2) levels in seminal plasma, but not in blood plasma, that was significantly associated with CP/CPPS and impaired urinary tract symptoms. In ejaculated somatic cells of CP/CPPS patients we found that ESR1 and ESR2 were both significantly higher methylated in CpG-promoters and expressionally down-regulated in comparison to controls. Mast cells are reported to contribute to CP/CPPS and are estrogen responsive. Consistent with this, we found that E2 -treatment of human mast cell lines (HMC-1 and LAD2) resulted in altered cytokine and chemokine expression. Interestingly, in HMC-1 cells, possessing epigenetically inactivated ESR1 and ESR2, E2 -treatment led to a reduced transcription of a number of inflammatory genes. Overall, these data suggest that elevated local E2 levels associate with an epigenetic down-regulation of the estrogen receptors and have a prominent role in CP/CPPS. Investigating E2 levels in semen could therefore serve as a promising biomarker to select patients for estrogen targeted therapy.

| S-EPMC5929413 | biostudies-literature

Targeting Src in endometriosis-associated ovarian cancer.

Project description:The SRC proto-oncogene is commonly overexpressed or activated during cancer development. Src family kinase inhibitors are approved for the treatment of certain leukemias, and are in clinical trials for the treatment of solid tumors. Src signaling is activated in endometriosis, a precursor of clear cell and endometrioid subtypes of epithelial ovarian cancers (OCs). We examined the expression of phosphorylated Src (Src-pY416) in 381 primary OC tissues. Thirty-six percent of OCs expressed Src-pY416. Src-pY416 expression was most common in endometriosis-associated OCs (EAOCs) (P=0.011), particularly in clear cell OCs where 58.5% of cases expressed Src-pY416. Src-pY416 expression was associated with shorter overall survival (log rank P=0.002). In vitro inhibition of Src signaling using 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo[3,4-d]pyrimidine (PP2) resulted in reduced anchorage-independent and -dependent growth, and in three-dimensional cell culture models PP2 disrupted aggregate formation in Src-pY416-positive but not in Src-pY416-negative cell lines. These data suggest that targeting active Src signaling could be a novel therapeutic opportunity for EAOCs, and support the further pre-clinical investigation of Src family kinase inhibitors for treating OCs expressing Src-pY416.

| S-EPMC5007828 | biostudies-literature

Microsatellites in the estrogen receptor (ESR1, ESR2) and androgen receptor (AR) genes and breast cancer risk in African American and Nigerian women.

Project description:Genetic variants in hormone receptor genes may be crucial predisposing factors for breast cancer, and microsatellites in the estrogen receptor (ESR1, ESR2) and androgen receptor (AR) genes have been suggested to play a role. We studied 258 African-American (AA) women with breast cancer and 259 hospital-based controls, as well as 349 Nigerian (NG) female breast cancer patients and 296 community controls. Three microsatellites, ESR1_TA, ESR2_CA and AR_CAG, in the ESR1, ESR2 and AR genes, respectively, were genotyped. Their repeat lengths were then analyzed as continuous and dichotomous variables. Analyses of continuous variables showed no association with breast cancer risk in either AA or NG at ESR1_TA; AA cases had shorter repeats in the long allele of ESR2_CA than AA controls (Mann-Whitney P= 0.036; logistic regression P = 0.04, OR= 0.91, 95% CI 0.83-1.00), whereas NG patients had longer repeats in the short allele than NG controls (Mann-Whitney P= 0.0018; logistic regression P= 0.04, OR= 1.06, 95% CI 1.00-1.11); and AA cases carried longer repeats in the short allele of AR_CAG than AA controls (Mann-Whitney P= 0.038; logistic regression P = 0.03, OR= 1.08, 95% CI 1.01-1.15). When allele sizes were categorized as dichotomous variables, we discovered that women with two long alleles of ESR2_CA had increased risk of breast cancer (OR = 1.38, 95% CI 1.10-1.74; P = 0.006). This is the first study to investigate these three microsatellites in hormonal receptor genes in relation to breast cancer risk in an indigenous African population. After adjusting for multiple-testing, our findings suggest that ESR2_CA is associated with breast cancer risk in Nigerian women, whereas ESR1_TA and AR_CAG seem to have no association with the disease among African American or Nigerian women.

| S-EPMC3394707 | biostudies-literature

GnRH dysregulation in polycystic ovarian syndrome (PCOS) is a manifestation of an altered neurotransmitter profile.

Project description:BACKGROUND:GnRH is the master molecule of reproduction that is influenced by several intrinsic and extrinsic factors such as neurotransmitters and neuropeptides. Any alteration in these regulatory loops may result in reproductive-endocrine dysfunction such as the polycystic ovarian syndrome (PCOS). Although low dopaminergic tone has been associated with PCOS, the role of neurotransmitters in PCOS remains unknown. The present study was therefore aimed at understanding the status of GnRH regulatory neurotransmitters to decipher the neuroendocrine pathology in PCOS. METHODS:PCOS was induced in rats by oral administration of letrozole (aromatase inhibitor). Following PCOS validation, animals were assessed for gonadotropin levels and their mRNA expression. Neurotrasnmitter status was evaluated by estimating their levels, their metabolism and their receptor expression in hypothalamus, pituitary, hippocampus and frontal cortex of PCOS rat model. RESULTS:We demonstrate that GnRH and LH inhibitory neurotransmitters - serotonin, dopamine, GABA and acetylcholine - are reduced while glutamate, a major stimulator of GnRH and LH release, is increased in the PCOS condition. Concomitant changes were observed for neurotransmitter metabolising enzymes and their receptors as well. CONCLUSION:Our results reveal that increased GnRH and LH pulsatility in PCOS condition likely result from the cumulative effect of altered GnRH stimulatory and inhibitory neurotransmitters in hypothalamic-pituitary centre. This, we hypothesise, is responsible for the depression and anxiety-like mood disorders commonly seen in PCOS women.

| S-EPMC5896071 | biostudies-literature

Association between polymorphisms in genes encoding estrogen receptors (ESR1 and ESR2) and excreted bisphenol A levels after orthodontic bracket bonding: a preliminary study.

Project description:BackgroundBisphenol A (BPA) is released from orthodontic composites used for bracket bonding. Genetic variations could modify the metabolism of this chemical within the organism. Considering that free BPA binds to estrogen receptors causing harmful effects to health, the present in vivo study aimed to evaluate the association between genetic polymorphisms in genes encoding estrogen receptors (ESR1 and ESR2) and excreted BPA levels in orthodontic patients.MethodsQuantification of BPA levels in the urine of 16 patients was performed in a gas chromatograph mass spectrometer before (T0), at 24 h (T1), and 1 week (T2) after bracket bonding. DNA was extracted from saliva, and one genetic polymorphism in ESR1 (rs2234693) and two in ESR2 (rs4986938 and rs1256049) were analyzed by real-time PCR. Increases in BPA levels in the urine at T1 and T2 were grouped according to the genotype, and mean differences were compared by unpaired T test or Mann-Whitney test according to the normality of the data. The established alpha was 5%.ResultsBPA levels increased significantly at T1 and T2. There were no statistically significant differences in the increases in BPA levels according to the genotype for any genetic polymorphism (P > 0.05), at neither 24 h nor 1 week after bracket bonding.ConclusionsThe results suggested that there are no association between excreted BPA levels after bracket bonding and the evaluated genetic polymorphisms in ESR1 and ESR2. Further research should be performed in order to confirm these results.

| S-EPMC6026583 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data