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Results for “Estrogen Receptor alpha”

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At least 19 recordsLinked to original sources

PubMed2004

Immunohistochemical analysis of estrogen receptor alpha, estrogen receptor beta and progesterone receptor in normal human endometrium.

The endometrium expresses estrogen (ER) and progesterone receptors (PR), which are involved in autocrine and paracrine regulation processes in response to estrogen and progesterone. The aim of the present study was to evaluate immunohistochemical distribution patterns of estrogen receptor alpha (ER alpha), estrogen receptor beta (ER beta) and PR in normal human endometrial tissue with the use of monoclonal antibodies. Human endometria were obtained from 17 premenopausal patients undergoing surgery for non-malignant diseases and were classified to be in proliferative, early secretory and late secretory phases by histological and anamnestical means. Distribution patterns of the steroid receptors were evaluated using the IRS-score and the Mann-Whitney rank-sum test was used to compare the means. Correlation was assessed with the Spearman factor and linear regression analysis. ER alpha and PR expression decreased significantly (p<0.05) in glandular epithelium from the proliferative to the late secretory phase. ER beta expression showed a similar significant decrease (p<0.05), although staining intensity was lower than that of ER alpha. A significant correlation between expression of all three steroid receptors was observed (p<0.001). Distribution patterns of ER alpha, ER beta and PR in normal human endometrium showed a cyclic variation during the menstrual cycle. A significant correlation between expression of ER alpha, ER beta and PR was also demonstrated using regression analysis, indicating dependence of expression of these three steroid receptors. The present study shows the presence of steroid receptors in human endometrial epithelium, indicating that these cells respond to estrogen and progesterone and thus playing a significant role in endometrial physiology.

Endometrium↗

PubMed2003

Expression and localization of estrogen receptor alpha, estrogen receptor beta and progesterone receptor in the bovine oviduct in vivo and in vitro.

This study examined the regulation and localization of estrogen receptors alpha and beta (ERalpha, ERbeta) and progesterone receptor (PR) in the bovine oviduct. Oviduct epithelial cells from cycling cows (in vivo) were investigated. In addition, the reactivity of a cell suspension culture stimulated with physiological doses of estradiol-17beta (E2) or progesterone (P4) was tested (in vitro). The specific steroid receptor expression of oviductal cells was quantified for mRNA using real-time RT-PCR. Furthermore, steroid receptor proteins were analyzed by Western blotting and localized by immunohistochemistry in situ. Obvious cyclic changes of receptor expression in vivo were observed and concurrent expression patterns were detected in vitro. PR and ERalpha mRNA transcripts were elevated in vivo during the follicular phase. The highest PR and ERalpha protein expression was detected subsequently during the early-luteal phase. In vitro, E2-supplementation resulted in an upregulation of PR and ERalpha. Both ERbeta mRNA and protein expression were highest during the luteal phase in vivo and elevated ERbeta expression levels were observed in vitro after P4 treatment. Evidence is provided for a varying expression of ERalpha, ERbeta and PR in bovine oviducts at different cycle stages in vivo, respectively under steroid supplementation in vitro. The region specific and cycle dependent expression differences point towards a functional importance of the three steroid receptors in the bovine oviduct, the site of fertilization and early embryonic development.

Animals↗

PubMedDate not supplied

Normal and malignant human endometrium express immunohistochemically estrogen receptor alpha (ER-alpha), estrogen receptor beta (ER-beta) and progesterone receptor (PR).

Human endometrium expresses estrogen (ER) and progesterone (PR) receptors, which are related to autocrine and paracrine processes that respond to estrogen and progesterone. The ER and PR expression and distribution pattern may play an important role in endometrial function and pathogenesis. The aim of this study was to evaluate the distribution pattern of ER-alpha, ER-beta and PR in normal (n=15) and malignant (n=11) human endometrial tissue. Commercially available monoclonal antibodies against ER-alpha, ER-beta and PR were used. The distribution of the steroid receptors was evaluated using the IRS-score and the Mann-Whitney rank-sum test was used to compare the means. Correlation was assessed with the Spearman factor and linear regression analysis. ER-alpha, ER-beta and PR declined significantly (p <0.05) in normal glandular epithelium from proliferative to late secretory phase, although the staining intensity of ER-beta was lower than that of ER-alpha. ER-alpha, ER-beta and PR were also expressed in malignant endometrial tissue. A significant correlation by regression analysis of ER-alpha and ER-beta was demonstrated, showing a dependence in the expression of these steroid receptors. The ER-alpha/ER-beta ratio decreased significantly from normal to malignant endometrial tissue (p<0.05), while the ER-beta/ER-alpha ratio showed statistical differences within normal endometrial tissue. These results showed the presence of steroid receptors in normal and malignant human endometrium, indicating a significant role in endometrial physiology and malignant transformation.

Endometrial Neoplasms↗

PubMed2006

[Expression of estrogen receptor-related receptor alpha and estrogen receptor alpha in endometrial carcinoma and the primary investigation of their clinical significance].

OBJECTIVE: To explore the roles of estrogen receptor-related receptor (ERR) alpha and estrogen receptor alpha in endometrial carcinoma and their clinical values. METHODS: Thirty-five cases of endometrial carcinoma were examined by immunohistochemistry. Clinicopathologic features including FIGO stage, histological grade, myometrial invasion and nodal metastasis were reviewed. RESULTS: The expression rate of ERalpha in patients with FIGO stage I endometrial carcinoma was more than that in stage II-IV(P = 0.005). The expression rate of ERRalpha in endometrial carcinoma patients at FIGO stage I was lower than that at stages II-IV(P = 0.007). The percentage of patients at FIGO stageI or with G1-2 or myometrial invasion < 1/2 in ERalpha (+) and ERRalpha (-) groups was higher than that in ERalpha (-) and ERRalpha (+) groups(P = 0.000, P = 0.031 and P = 0.022). CONCLUSION: ERalpha may be a biomarker of good prognosis while ERRalpha may serve as a biomarker of poor prognosis in endometrial carcinoma. The combinative measure of ERalpha and ERRalpha may improve the prognostic value.

Adenocarcinoma↗

PubMed2002

Differential expression of estrogen receptor-related receptor alpha and estrogen receptors alpha and beta in osteoblasts in vivo and in vitro.

The orphan nuclear estrogen receptor-related receptor (ERR) alpha is expressed by osteoblastic cells, is known to transactivate at least one osteoblast-associated gene osteopontin (OPN) and plays a functional role in osteoprogenitor cell proliferation and differentiation. To dissect further the role of ERR-alpha in bone formation, we compared its expression to that of the estrogen receptor (ER) alpha and ER-beta in rat calvaria (RC) and fetal tibia in vivo and in RC and rat bone marrow (RBM) cells in vitro. We found that ERR-alpha is highly and widely expressed in most, if not all, cells in RC cell cultures from early proliferation stages through mineralized nodule formation; ER-alpha was localized similarly but at lower levels and ER-beta, although present, was barely detectable. These patterns of expression in vitro correlated with what we observed in vivo in sections of 21-day fetal RC, in which ERR-alpha appeared to be more highly expressed than either of the ERs. Interestingly, ERR-a also is highly expressed in RBM cells, while ER-alpha and ER-beta mRNA is expressed, but at lower levels. Moreover, we found that ERR-alpha, ER-alpha, and ER-beta were all expressed in osteoblasts in fetal and adult tibia whereas they were expressed differentially in calvaria in vivo in subsets of osteoblasts, supporting the hypothesis that ERR-alpha may interact with one or both of the ERs in those osteoblasts in which they are coexpressed and that all three receptors may be required for bone formation but at different times and for different functions.

Animals↗

PubMed2003

Immunolocalization of estrogen receptor beta in the mouse brain: comparison with estrogen receptor alpha.

Estrogen receptor alpha (ER alpha) and ER beta are members of the steroid nuclear receptor family that modulate gene transcription in an estrogen-dependent manner. ER mRNA and protein have been detected both peripherally and in the central nervous system, with most data having come from the rat. Here we report the development of an ER beta-selective antibody that cross-reacts with mouse, rat, and human ER beta protein and its use to determine the distribution of ER beta in the murine brain. Further, a previously characterized polyclonal antibody to ER alpha was used to compare the distribution of the two receptors in the first comprehensive description of ER distribution specifically in the mouse brain. ER beta immunoreactivity (ir) was primarily localized to cell nuclei within select regions of the brain, including the olfactory bulb, cerebral cortex, septum, preoptic area, bed nucleus of the stria terminalis, amygdala, paraventricular hypothalamic nucleus, thalamus, ventral tegmental area, substantia nigra, dorsal raphe, locus coeruleus, and cerebellum. Extranuclear-ir was detected in several areas, including fibers of the olfactory bulb, CA3 stratum lucidum, and CA1 stratum radiatum of the hippocampus and cerebellum. Although both receptors were generally expressed in a similar distribution through the brain, nuclear ER alpha-ir was the predominant subtype in the hippocampus, preoptic area, and most of the hypothalamus, whereas it was sparse or absent from the cerebral cortex and cerebellum. Collectively, these findings demonstrate the region-selective expression of ER beta and ER alpha in the adult ovariectomized mouse brain. These data provide an anatomical framework for understanding the mechanisms by which estrogen regulates specific neural systems in the mouse.

Amino Acid Sequence↗

PubMed1998

DNA-binding properties of the overexpressed recombinant estrogen receptor alpha.

Estrogen receptor alpha was overexpressed in COS-7 cells by transformation of an expression vector with the full length open reading frame of the receptor alpha. The nuclear estradiol-receptor complex and the soluble receptor from the COS-7 cells were cross-linked with an estrogen response element (ERE), which was substituted with 5-bromo-2'-deoxyuridine (BrdUVRE), as the receptor dimers by UV irradiation. In gel retardation analysis, the specific bindings of both nuclear and soluble receptors to ERE were decreased with increasing of KCl concentration compared with 0.1 M KCl. The ionic interactions of both receptors with ERE are thought to be similar.

Animals↗

PubMed2003

Aggression in male mice lacking functional estrogen receptor alpha.

Estrogen receptor alpha knockout (ERaKO) male mice fail to display sexual behavior. The authors hypothesized that ERalphaKOs require higher testosterone (T) concentrations than wild-type (WT) males to exhibit copulatory behavior. Increasing T stimulated sexual behavior and preference for females in WT males but failed to do so in ERalphaKOs. However, T did induce female-directed aggression in ERaKOs. In aggression tests, WT residents selectively attacked T-treated male intruders. ERaKO residents attacked female, T-treated male, and estrogen-treated male intruders equally. Increased access to olfactory cues prior to direct contact reduced overall aggression in ERalphaKO versus WT males but did not cause ERalphaKOs to differentially attack male and female opponents. Results suggest that ERalpha is essential for normal social behavior, perhaps via processing of chemoinvestigatory cues, which are required to discriminate males from females.

Aggression↗

PubMed2000

Dopamine activates masculine sexual behavior independent of the estrogen receptor alpha.

Estrogen receptor alpha (ERalpha) is believed to be a critical part of the regulatory processes involved in normal reproduction and sexual behavior. However, in this study we show the ERalpha is not required for display of masculine sexual behavior. Male and female, ERalpha knock-out (ERalphaKO) and wild-type mice were gonadectomized and implanted with testosterone. Sexual behavior and social preferences were tested after injection of the dopamine agonist, apomorphine (APO), or vehicle. All wild-type mice showed normal masculine behavior, including mounts and pelvic thrusts in females, and ejaculation in males. In agreement with past reports, ERalphaKO mice, given vehicle, failed to show mating behavior. Yet, ERalphaKO males given APO showed masculine copulatory behavior and chemoinvestigatory behavior directed at females. ERalphaKO females, treated with APO, mounted and thrusted when tested with receptive females. HPLC revealed that wild-type and ERalphaKO mice had equivalent catecholamine content in brain regions associated with masculine sexual behavior. These data show that the ERalpha is not essential during development or adulthood for the expression of masculine sexual behavior in mice. Moreover, dopamine can activate sexual behavior via a mechanism that either acts on an ER other than ERalpha or via an estrogen-independent pathway.

Animals↗

PubMed2006

Both estrogen receptor alpha and estrogen receptor beta agonists enhance cell proliferation in the dentate gyrus of adult female rats.

This study investigated the involvement of estrogen receptors alpha and beta in estradiol-induced enhancement of hippocampal neurogenesis in the adult female rat. Subtype selective estrogen receptor agonists, propyl-pyrazole triol (estrogen receptor alpha agonist) and diarylpropionitrile (estrogen receptor beta agonist) were examined for each receptor's contribution, individual and cooperative, for estradiol-enhanced hippocampal cell proliferation. Estradiol increases hippocampal cell proliferation within 4 h [Ormerod BK, Lee TT, Galea LA (2003) Estradiol initially enhances but subsequently suppresses (via adrenal steroids) granule cell proliferation in the dentate gyrus of adult female rats. J Neurobiol 55:247-260]. Therefore, animals received s.c. injections of estradiol (10 microg), propyl-pyrazole triol and diarylpropionitrile alone (1.25, 2.5, 5.0 mg/0.1 ml dimethylsulfoxide) or in combination (2.5 mg propyl-pyrazole triol+2.5 mg diarylpropionitrile/0.1 ml dimethylsulfoxide) and 4 h later received an i.p. injection of the cell synthesis marker, bromodeoxyuridine (200 mg/kg). Diarylpropionitrile enhanced cell proliferation at all three administered doses (1.25 mg, P<0.008; 2.5 mg, P<0.003; 5 mg, P<0.005), whereas propyl-pyrazole triol significantly increased cell proliferation (P<0.0002) only at the dose of 2.5 mg. Our results demonstrate both estrogen receptor alpha and estrogen receptor beta are individually involved in estradiol-enhanced cell proliferation. Furthermore both estrogen receptor alpha and estrogen receptor beta mRNA was found co-localized with Ki-67 expression in the hippocampus albeit at low levels, indicating a potential direct influence of each receptor subtype on progenitor cells and their progeny. Dual receptor activation resulted in reduced levels of cell proliferation, supporting previous studies suggesting that estrogen receptor alpha and estrogen receptor beta may modulate each other's activity. Our results also suggest that a component of estrogen receptor-regulated cell proliferation may take place through alternative ligand and/or cell-signaling mechanisms.

Analysis of Variance↗

PubMed2006

Expression of estrogen receptor-alpha, estrogen receptor-beta and placental endothelial and inducible NO synthase in intrauterine growth-restricted and normal placentals.

BACKGROUND: Nitric oxide seems to play important roles in the physiology of placental blood circulation, although their expression in pathological placentas and their role is still unclear. Therefore, the aim of this study was to investigate the expression of estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta) and the endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) in intrauterine growth-restricted (IUGR) placentas, hemolysis, elevated liver enzymes, low platelets (HELLP) placentas and in normal healthy control placentas. METHODS: Slides of paraffin-embedded placental tissue were obtained after delivery from patients diagnosed with IUGR, HELLP and normal term placentas and analyzed for eNOS and iNOS, as well as ERalpha/beta expression. Intensity of immunohistochemical reaction was analyzed using a semi-quantitative score, and statistical analysis was performed. In addition, Western blot experiments were performed for comparison of staining intensities obtained by immunohistochemistry and Western blot. RESULTS: Expression of eNOS and iNOS is significantly reduced in trophoblast cells of placentas with HELLP. However, ERbeta expression in HELLP placentas demonstrated a significantly elevated expression intensity compared to normal controls. ERalpha expression was not significantly different in all three pathologies investigated. CONCLUSIONS: We speculate that the increased ERbeta expression in both syncytiotrophoblast and extravillous trophoblast cells represents accelerated proliferation of placental tissue or can be seen as a compensatory effect in HELLP placentas.

Estrogen Receptor alpha↗

PubMed2005

Estrogen activates rapid signaling in the brain: role of estrogen receptor alpha and estrogen receptor beta in neurons and glia.

The aging process is known to coincide with a decline in circulating sex hormone levels in both men and women. Due to an increase in the average lifespan, a growing number of post-menopausal women are now receiving hormone therapy for extended periods of time. Recent findings of the Women's Health Initiative, however, have called into question the benefits of long-term hormone therapy for treating symptoms of menopause. The results of this study are still being evaluated, but it is clear that a better understanding of the molecular effects of estradiol is needed in order to develop new estrogenic compounds that activate specific mechanisms but lack adverse side effects. Traditionally, the effects of estradiol treatment have been ascribed to changes in gene expression, namely transcription at estrogen response elements. This review focuses on emerging information that estradiol can also activate a repertoire of membrane-initiated signaling pathways and that these rapid signaling events lead to functional changes at the cellular level. The various types of cells in the brain can respond differently to estradiol treatment based on the signaling properties of the cell, as well as which receptor, estrogen receptor alpha and/or estrogen receptor beta, is expressed. Taken together, these findings suggest that the estradiol-induced activation of membrane-initiated signaling pathways occurs in a cell-type specific manner and can differentially influence how the cells respond to various insults.

Animals↗

PubMed2001

Re-expression of estrogen receptor alpha in estrogen receptor alpha-negative MCF-7 cells restores both estrogen and insulin-like growth factor-mediated signaling and growth.

Estrogen can increase insulin-like growth factor-I receptor (IGF-IR) and insulin receptor substrate-1 (IRS-1) expression, two key components of IGF-I-mediated signaling. The result is sensitization of breast cancer cells to IGF-I and synergistic growth in the presence of estrogen and IGF-I. We hypothesized that loss of estrogen receptor alpha (ERalpha) would result in reduced IGF-mediated signaling and growth. To test this hypothesis, we examined IGF-I effects in MCF-7 breast cancer cell sublines that have been selected for loss of ERalpha (C4 and C4-12 cells are ERalpha-negative) by long-term estrogen withdrawal. C4 and C4-12 cells had reduced IGF-IR and IRS-1 mRNA and protein expression (compared with MCF-7 cells) that was not inducible by estrogen. Furthermore, C4 and C4-12 cells showed reduced IGF-I signaling and failed to show any growth response to either estrogen or IGF-I. To prove that loss of IGF and estrogen-mediated signaling and growth was a consequence of loss of ERalpha, we re-expressed ERalpha in C4-12 cells by stable transfection with HA-tagged ERalpha. Three independent C4-12 ERalpha-HA clones expressed a functional ERalpha that (a) was down-regulated by estrogen, (b) conferred estrogen-induction of cyclin D1 expression, and (c) caused estrogen-mediated increase in the number of cells in S phase. All of the effects were completely blocked by antiestrogens. Interestingly, ERalpha-HA expression in C4-12 cells did not restore estrogen induction of progesterone receptor expression. However, ERalpha-positive C4-12 cells now exhibited estrogen-induction of IGF-IR and IRS-1 levels and responded mitogenically to both estrogen and IGF-I. These data show that ERalpha is a critical requirement for IGF signaling, and to our knowledge this is the first report of functional ERalpha expression that confers estrogen-mediated growth of an ER-negative breast cancer cell line.

Breast Neoplasms↗

PubMed2004

Post-hatching syrinx development in the zebra finch: an analysis of androgen receptor, aromatase, estrogen receptor alpha and estrogen receptor beta mRNAs.

In zebra finches, the vocal organ (syrinx) is larger in males than in females. Specific details about the mechanisms responsible for this dimorphism are not known, but may involve sex differences in steroid hormone action early in post-hatching development. The distribution of androgen receptor (AR), aromatase (AROM), estrogen receptor alpha (ERalpha), and estrogen receptor beta (ERbeta) mRNAs was examined at post-hatching days 3, 10 and 17. A low level of AR was equivalently expressed in the syrinx muscles of both sexes at all three ages. We detected no specific expression of AROM or ERalpha mRNAs. In contrast, ERbeta mRNA was detected in chondrocytes of the forming bone. The density of this expression increased with age as the chondrocytes hypertrophied, but did not differ between the sexes. Taken together, these data suggest that estrogens may act on cartilage/bone, and androgens may act on muscle fibers in early post-hatching development to influence syrinx morphology. However, the lack of a sex difference in steroid receptor mRNA expression in the syrinx suggests that, similar to the forebrain regions that control song, the interaction of androgens and estrogens with their receptors is not sufficient to induce full sexual differentiation of this organ.

Aging↗

PubMed1998

Differential response of estrogen receptor alpha and estrogen receptor beta to partial estrogen agonists/antagonists.

The existence of two rather than one estrogen receptor, today characterized as estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta), indicates that the mechanism of action of 17beta-estradiol and related synthetic drugs is more complex than previously thought. Because the homology of amino acid residues in the ligand-binding domain (LBD) of ERbeta is high compared with those amino acid residues in ERalpha LBD, previously shown to line the ligand binding cavity or to make direct contacts with ligands, it is not surprising that many ligands have a similar affinity for both receptor subtypes. We report that 17alpha-ethynyl, 17beta-estradiol, for example, has an ERalpha-selective agonist potency and that 16beta,17alpha-epiestriol has an ERbeta-selective agonist potency. We also report that genistein has an ERbeta-selective affinity and potency but an ERalpha-selective efficacy. Furthermore, we show that tamoxifen, 4-OH-tamoxifen, raloxifene, and ICI 164,384 have an ERalpha-selective partial agonist/antagonist function but a pure antagonist effect through ERbeta. In addition, raloxifene displayed an ERalpha-selective antagonist potency, in agreement with its ERalpha-selective affinity. However, although ICI 164,384 showed an ERbeta-selective affinity, it had a similar potency to antagonize the effect of 17beta-estradiol in the ERalpha- and ERbeta-specific reporter cell lines, respectively. In conclusion, our data indicate that the ligand binding cavity of ERbeta is probably more different from that of ERalpha than can be anticipated from the primary sequences of the two ER subtypes and that it will be possible to develop receptor-specific ligands that may form the basis of novel pharmaceuticals with better in vivo efficacy and side effect profile than current available drugs.

Cells, Cultured↗

PubMedDate not supplied

The expression of aromatase, estrogen receptor alpha and estrogen receptor beta in mouse Leydig cells in vitro that derived from cryptorchid males.

A broad expression of aromatase and estrogen receptors (ERs) in the testis suggests an important role for estrogens in regulating testicular cell function and reproductive events. The aim of the present study was to show whether Leydig cells in vitro isolated from cryptorchid testes of two inbred strains of mice, KE and CBA, are a site of estrogen synthesis. Using immunocytochemistry, aromatase, estrogen receptor alpha(ERalpha), and estrogen receptor beta(ERbeta) were localized in cultured Leydig cells. Immunoreactive aromatase was found in the cytoplasm of control Leydig cells and those isolated from cryptorchid males, however the intensity of immunostaining was different, being stronger in Leydig cells deriving from cryptorchid mice. The strongest aromatase immunostaining was found in cryptorchid-KE Leydig cells. Strong immunoexpression of ERalpha was detected in the nuclei of both KE-and CBA-Leydig cells. The intensity of ERalpha immunostaining was stronger in cultured cells deriving from cryptorchid testes. ERbeta immunoexpression was detected predominantly in KE-Leydig cells. Control CBA-Leydig cells were negative for ERbeta or the result was inconclusive, whereas in cryptorchid CBA-Leydig cells a weak immunostaining was present in their nuclei. Western blot analysis confirmed the results obtained by immunocytochemistry. In KE- and CBA-Leydig cells aromatase as a band of 55 kDa protein was present, whereas ERalpha molecular weight was 67 kDa on Western blots. No band was detected for ERbeta. Radioimmunological analysis revealed that androgen and estrogen levels secreted by Leydig cells in vitro were strain-dependent. Additionally, in KE-Leydig cells that derived from cryptorchid mice estrogen level was distinctly higher in comparison with that of the respective control.

Animals↗

PubMed2005

p21WAF1/CIP1 selectively controls the transcriptional activity of estrogen receptor alpha.

Estrogen receptors (ER) are ligand-dependent transcription factors that regulate growth, differentiation, and maintenance of cellular functions in a wide variety of tissues. We report here that p21WAF1/CIP1, a cyclin-dependent kinase (Cdk) inhibitor, cooperates with CBP to regulate the ERalpha-mediated transcription of endogenous target genes in a promoter-specific manner. The estrogen-induced expression of the progesterone receptor and WISP-2 mRNA transcripts in MCF-7 cells was enhanced by p21WAF1/CIP1, whereas that of the cyclin D1 mRNA was reduced and the pS2 mRNA was not affected. Chromatin immunoprecipitation assays revealed that p21WAF1/CIP1 was recruited simultaneously with ERalpha and CBP to the endogenous progesterone receptor gene promoter in an estrogen-dependent manner. Experiments in which the p21WAF1/CIP1 protein was knocked down by RNA interference showed that the induction of the expression of the gene encoding the progesterone receptor required p21WAF1/CIP1, in contrast with that of the cyclin D1 and pS2 genes. p21WAF1/CIP1 induced not only cell cycle arrest in breast cancer cells but also milk fat globule protein and lipid droplets, indicators of the differentiated phenotype, as well as cell flattening and increase of the volume of the cytoplasm. These results indicate that p21WAF1/CIP1, in addition to its Cdk-regulatory role, behaves as a transcriptional coactivator in a gene-specific manner implicated in cell differentiation.

Breast Neoplasms↗

PubMed2000

Nongenomic actions of estrogens and xenoestrogens by binding at a plasma membrane receptor unrelated to estrogen receptor alpha and estrogen receptor beta.

The molecular mechanism used by environmental chemicals to exert their hormone-like actions is still only partially resolved. Although it generally is accepted that xenoestrogens act at the genomic level by binding to intracellular estrogen receptors, we have shown here that they trigger nongenomic effects in pancreatic beta cells. Both xenoestrogens and the circulating hormone, 17beta-estradiol, bind with high affinity to a common membrane binding site unrelated to the intracellular estrogen receptors ERalpha and ERbeta. This binding site is shared by dopamine, epinephrine, and norepinephrine and has the pharmacological profile of the gammaadrenergic receptor. This study provides an outline of the membrane receptor involved in rapid xenoestrogen actions.

Animals↗