Transcription profiling of human estrogen-responsive breast cancer cell lines treated with 17beta-estradiol for 1 to 32 hours
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Wu HY
PROVIDER: S-ECPF-TABM-742 | biostudies-other | 2012
REPOSITORIES: biostudies-other
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Project description:Human estrogen-responsive breast cancer cell lines ZR-75-1 and MCF-7 were treated with 10nM of 17beta-estradiol. Gene expression was analyzed on total RNA extracted before or after 1, 2, 4, 6, 8, 12, 16, 20, 24, 28 and 32 hours hormonal stimulation. For each condition 2 technical replicates were performed, except the reference sample (before stimulation - 0h) which was in respectively in quadruplicate and quintuplicate.
2010-01-11 | E-TABM-742 | biostudies-arrayexpress
Project description:Human estrogen-responsive breast cancer cell line ZR-75-1 was treated with 10nM of 17 beta-estradiol. Gene expression was analyzed on total RNA extracted before or after 1, 2, 4, 6, 8, 12, 16, 20, 24, 28 and 32 hours hormonal stimulation. For each condition 2 technical replicates were performed, except the reference sample (before stimulation - 0h) which was in quadruplicate and the 4h sample in triplicate.
| S-ECPF-TABM-631 | biostudies-other
Project description:Gene expression changes caused by estrogen treatment of breast cancer cells that re-express ERalpha was investigated by infecting ER-negative MDA-MB-231 breast cancer cells for 24 h with recombinant adenovirus encoding full-length human ERalpha (Ad-ERalpha) or control vector (Ad-LacZ), and treating them with 0·01% ethanol (vehicle control) or 10-8 M 17beta-estradiol (E2). After 48 h of treatment, total RNA was isolated and used for transcript profiling on Affymetrix GeneChips. Three independent biological replicates of this experiment were carried out.
| S-ECPF-GEOD-2251 | biostudies-other
Project description:Estrogen can significantly influence CD16 expression and alter monocytic cytokine release upon CD16 receptor activation. However, the function of the estrogen receptor (ER) alpha and beta in this response is unclear. To test whether estrogen binds ERalpha and/or ERbeta to affect CD16 expression, monocytic cells were treated with and without physiological levels of 17beta-estradiol and various doses of the ERalpha and ERbeta antagonist fulvestrant followed by measurement of CD16 transcript levels. To determine how estrogen induced changes in TNF-alpha and IL-1beta release due to CD16 activation we quantitated the amount of cytokines after treatment with estrogen, fulvestrant and antibodies that specifically bind and activate the CD16 receptor. Interaction of ERalpha and the CD16 promoter was then determined by chromatin immunoprecipitation. Furthermore, specific promoter elements utilized by estrogen to control CD16 expression were mutated and expression from a luciferase reporter quantitated after transfection. Using the luciferase reporter construct containing a wild type CD16 promoter, the role of ERalpha and ERbeta in the estrogen response was tested by treating transfected monocytes with an ERalpha specific agonist or an ERbeta specific agonist and measuring expression. Our results show that CD16 transcript levels significantly decreased in monocytic cells due to estrogen and that the observed decrease in message was blocked by the antagonist fulvestrant. Estrogen reduced CD16 expression and decreased TNF-alpha and IL-1beta release upon CD16 activation but the administration of fulvestrant blocked this decrease. ERalpha was found to interact with a region 5' of the CD16 gene in the presence of estrogen, and site-directed mutational analysis of this region indicated the necessity for an estrogen response element in modulating estrogen effects on CD16 expression. Moreover, both an ERalpha and an ERbeta agonist reduced expression of the CD16 reporter construct suggesting both receptors can play a role in CD16 regulation. In conclusion, CD16 expression can be altered by the activity of ERalpha or ERbeta and our results also show that ERalpha can associate with a region within the CD16 promoter that is important in production of transcript.
| S-EPMC2128779 | biostudies-literature
Project description:17?-estradiol (E2) plays a key role in tumorigenesis by enhancing cell survivability and metastasis through its cytoplasmic receptors. Recently, a variant of estrogen receptor alpha, ER?36 has been implicated as a substantial mediator of E2's proliferative and antiapoptotic effects through rapid membrane-associated signaling, and cancers previously regarded as hormone-independent due to the absence of traditional receptors, may in fact be susceptible to E2. Despite rising from a secondary sex organ and having a clear gender disposition, laryngeal cancer is not uniformly accepted as hormone dependent, even in the face of compelling evidence of E2 responsiveness. The aim of this study was to further elucidate the role of E2 in the tumorigenesis of laryngeal cancer, both in vitro and in vivo. ER?36 presence was evaluated in membranes of the laryngeal carcinoma cell line, Hep2, as well as in laryngeal tumor samples. In vitro ER?36 was found to mediate rapid activation of protein kinase C and phospholipase D by E2, leading to increased proliferation and protection against chemotherapy-induced apoptosis. Furthermore, in response to E2 activation of ER?36, an upregulation of angiogenic and metastatic factors was observed. Clinical analysis of laryngeal tumors revealed a similar association between the amount of ER?36 and VEGF and indicated a role in lymph node metastasis. These findings present compelling evidence of ER?36-dependent E2 signaling in laryngeal cancer. Thus, targeting ER?36 may reduce the deleterious effects of E2 in laryngeal cancer, ultimately suggesting the importance of antiestrogen therapy or the production of novel drugs that specifically target ER?36.
| S-EPMC3947116 | biostudies-literature
Project description:A series of MCF-7 variants were previously developed that are either estrogen-dependent for growth (MCF-7:WS8 cells), or resistant to estrogen deprivation and refractory (MCF-7:2A) or sensitive (MCF-7:5C) to E2-induced apoptosis. To identify genes associated with E2-induced apoptosis, estrogen deprivation-resistant/apoptotic-sensitive 5C cells were compared to both estrogen-dependent MCF-7:WS8 and estrogen deprivation/apoptotic-refractory MCF-7:2A cells Each cell line was treated with 10-9 M E2 or vehicle control over a 96 h time course consisting of 7 time points (2, 6, 12, 24, 48, 72 and 96 h) using 6 biological replicates per condition. cRNA probes from individual E2-treated samples were competitively hybridized against time-matched pooled control probes using 2-color Agilent 4x44k human oligonucleotide microarrays.
| S-ECPF-GEOD-29917 | biostudies-other
Project description:Full-length 66-kDa estrogen receptor alpha (ERalpha) stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal domain and AF-2 in the ligand binding domain. Another physiologically expressed 46-kDa ERalpha isoform lacks the N-terminal A/B domains and is consequently devoid of AF-1. Previous studies in cultured endothelial cells showed that the N-terminal A/B domain might not be required for estradiol (E2)-elicited NO production. To evaluate the involvement of ERalpha AF-1 in the vasculoprotective actions of E2, we generated a targeted deletion of the ERalpha A/B domain in the mouse. In these ERalphaAF-1(0) mice, both basal endothelial NO production and reendothelialization process were increased by E2 administration to a similar extent than in control mice. Furthermore, exogenous E2 similarly decreased fatty streak deposits at the aortic root from both ovariectomized 18-week-old ERalphaAF-1(+/+) LDLr(-/-) (low-density lipoprotein receptor) and ERalphaAF-1(0) LDLr (-/-) mice fed with a hypercholesterolemic diet. In addition, quantification of lesion size on en face preparations of the aortic tree of 8-month-old ovariectomized or intact female mice revealed that ERalpha AF-1 is dispensable for the atheroprotective action of endogenous estrogens. We conclude that ERalpha AF-1 is not required for three major vasculoprotective actions of E2, whereas it is necessary for the effects of E2 on its reproductive targets. Thus, selective ER modulators stimulating ERalpha with minimal activation of ERalpha AF-1 could retain beneficial vascular actions, while minimizing the sexual effects.
| S-EPMC2644162 | biostudies-literature
Project description:Low-voltage-activated (T-type) calcium channels are responsible for burst firing and transmitter release in neurons and are important for exocytosis and hormone secretion in pituitary cells. T-type channels contain an alpha1 subunit, of which there are three subtypes, Cav3.1, -3.2, and -3.3, and each subtype has distinct kinetic characteristics. Although 17beta-estradiol (E2) modulates T-type calcium channel expression and function, little is known about the molecular mechanisms involved. We used real-time PCR quantification of RNA extracted from hypothalamic nuclei and pituitary in vehicle and E2-treated C57BL/6 mice to elucidate E2-mediated regulation of Cav3.1, -3.2, and -3.3 subunits. The three subunits were expressed in both the hypothalamus and the pituitary. E2 treatment increased the mRNA expression of Cav3.1 and -3.2, but not Cav3.3, in the medial preoptic area and the arcuate nucleus. In the pituitary, Cav3.1 was increased with E2 treatment, and Cav3.2 and -3.3 were decreased. To examine whether the classical estrogen receptors (ERs) were involved in the regulation, we used ERalpha- and ERbeta-deficient C57BL/6 mice and explored the effects of E2 on T-type channel subtypes. Indeed, we found that the E2-induced increase in Cav3.1 in the hypothalamus was dependent on ERalpha, whereas the E2 effect on Cav3.2 was dependent on both ERalpha and ERbeta. However, the E2-induced effects in the pituitary were dependent on only the expression of ERalpha. The robust E2 regulation of T-type calcium channels could be an important mechanism by which E2 increases the excitability of hypothalamic neurons and modulates pituitary secretion.
| S-EPMC2821194 | biostudies-literature
Project description:Estrogen is atheroprotective and a high-affinity ligand for both known estrogen receptors, ERalpha and ERbeta. However, the role of the ERalpha in early-stage atherosclerosis has not been directly investigated and is incompletely understood. ERalpha-deficient (ERalpha-/-) and wild-type (ERalpha+/+) female mice consuming an atherogenic diet were studied concurrent with estrogen replacement to distinguish the actions of 17beta-estradiol (E(2)) from those of ERalpha on the development of early atherosclerotic lesions. Mice were ovariectomized and implanted with subcutaneous slow-release pellets designed to deliver 6 or 8 mug/day of exogenous 17beta-estradiol (E(2)) for a period of up to 4 months. Ovariectomized mice (OVX) with placebo pellets (E(2)-deficient controls) were compared to mice with endogenous E(2) (intact ovaries) and exogenous E(2). Aortas were analyzed for lesion area, number, and distribution. Lipid and hormone levels were also determined. Compared to OVX, early lesion development was significantly (p < 0.001) attenuated by E(2) with 55-64% reduction in lesion area by endogenous E(2) and >90% reduction by exogenous E(2). Compared to OVX, a decline in lesion number (2- to 4-fold) and lesser predilection (~4-fold) of lesion formation in the proximal aorta also occurred with E(2). Lesion size, development, number, and distribution inversely correlated with circulating plasma E(2) levels. However, atheroprotection was independent of ERalpha status, and E(2) athero-protection in both genotypes was not explained by changes in plasma lipid levels (total cholesterol, triglyceride, and high-density lipoprotein cholesterol). The ERalpha is not essential for endogenous/exogenous E(2)-mediated protection against early-stage atherosclerosis. These observations have potentially significant implications for understanding the molecular and cellular mechanisms and timing of estrogen action in different estrogen receptor (ER) deletion murine models of atherosclerosis, as well as implications to human studies of ER polymorphisms and lipid metabolism. Our findings may contribute to future improved clinical decision-making concerning the use of hormone therapy.
| S-EPMC2719738 | biostudies-other
Project description:One area of great importance in breast cancer (BC) research is the study of gene expression regulated by both estrogenic and antiestrogenic agents. Although many studies have been performed in this area, most of them have only addressed the effects of 17β-estradiol (E2) and tamoxifen (TAM) on MCF7 cells. This study aimed to determine the effect of low doses of E2 and TAM on the expression levels of 84 key genes, which are commonly involved in breast carcinogenesis, in four BC cell lines differentially expressing estrogen receptor (ER) α and HER2 (MCF7, T47D, BT474, and SKBR3). The results allowed us to determine the expression patterns modulated by E2 and TAM in ERα+ and ERα- cell lines, as well as to identify differences in expression patterns. Although the MCF7 cell line is the most frequently used model to determine gene expression profiles in response to E2 and TAM, the changes in gene expression patterns identified in ERα+ and ERα- cell lines could reflect distinctive properties of these cells. Our results could provide important markers to be validated in BC patient samples, and subsequently used for predicting the outcome in ERα+ and ERα- tumors after TAM or hormonal therapy. Considering that BC is a molecularly heterogeneous disease, it is important to understand how well, and which cell lines, best model that diversity.
| S-EPMC5614746 | biostudies-literature