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Eva Kassi,
George P Chrousos,
Eleni Melliou,
Chunyan Zhao,
Karin Dahlman-Wright,
Paraskevi Moutsatsou,
Andrey Karshikoff,
Anna Tsiapara,
Nina Heldring,
Ioanna Chinou,
Zoi Papoutsi, Lennart Nilsson
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Marko Matic,
Galyna Bryzgalova,
Hui Gao,
Per Antonson,
Patricia Humire,
Yoko Omoto,
Neil Portwood,
Camilla Pramfalk,
Suad Efendic,
Per-Olof Berggren,
Jan-Åke Gustafsson, Karin Dahlman-Wright
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ABSTRACT: An increasing body of evidence now links estrogenic signalling with the metabolic syndrome (MS). Despite the beneficial estrogenic effects in reversing some of the MS symptoms, the underlying mechanisms remain largely undiscovered. We have previously shown that total estrogen receptor alpha (ERα) knockout (KO) mice exhibit hepatic insulin resistance. To determine whether liver-selective ablation of ERα recapitulates metabolic phenotypes of ERKO mice we generated a liver-selective ERαKO mouse model, LERKO. We demonstrate that LERKO mice have efficient reduction of ERα selectively within the liver. However, LERKO and wild type control mice do not differ in body weight, and have a comparable hormone profile as well as insulin and glucose response, even when challenged with a high fat diet. Furthermore, LERKO mice display very minor changes in their hepatic transcript profile. Collectively, our findings indicate that hepatic ERα action may not be the responsible factor for the previously identified hepatic insulin resistance in ERαKO mice.
PLoS ONE 01/2013; 8(2):e57458. · 4.09 Impact Factor
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ABSTRACT: Estrogen receptor-α (ERα) is initially overexpressed in two-thirds of all breast cancer and is involved in its development and proliferation. We previously reported that the RBCC protein interacting with PKC 1 (RBCK1) interacts with the ERα promoter and that RBCK1 expression positively correlates with ERα levels, expression of ERα downstream target genes and proliferation of breast cancer cells. Based on this, and that RBCK1 positively correlates with ERα expression in breast cancer samples, we propose RBCK1 as a potential therapeutic target in breast cancer acting as a modulator of ERα expression. To further explore this, the molecular mechanism by which RBCK1 regulates ERα expression has to be defined. Here, we show that ERα, RBCK1 and the RBCK1-interacting protein Protein Kinase C beta 1 (PKCβI) co-occupy a previously identified ERα binding region in the proximal ERα promoter. We describe a number of mechanistic details of this complex including that RBCK1 recruitment to the ERα promoter B is facilitated by ERα, which in turn facilitates PKCβI recruitment and PKCβI-dependent histone modifications. Furthermore, ERα regulation of its own mRNA expression is facilitated by RBCK1 recruitment, suggesting an ERα coactivator function of RBCK1 The interaction between RBCK1 and ERα was dependent on the E3 ubiquitin ligase domain of RBCK1 and the AF-1 domain of ERα. The ligand-binding function of ERα does not influence the interaction with RBCK1. In summary, our data provide insight into the molecular mechanism by which ERα expression is modulated in breast cancer cells.
Journal of Molecular Endocrinology 10/2012; · 3.48 Impact Factor
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ABSTRACT: Estrogen signaling and epigenetic modifications, in particular DNA methylation, are involved in regulation of gene expression in breast cancers. Here we investigated a potential regulatory cross-talk between these two pathways by identifying their common target genes and exploring underlying molecular mechanisms in human MCF-7 breast cancer cells. Gene expression profiling revealed that the expression of approximately 140 genes was influenced by both 17β-estradiol (E2) and a demethylating agent 5-aza-2'-deoxycytidine (DAC). Gene ontology (GO) analysis suggests that these genes are involved in intracellular signaling cascades, regulation of cell proliferation and apoptosis. Based on previously reported association with breast cancer, estrogen signaling and/or DNA methylation, CpG island prediction and GO analysis, we selected six genes (BTG3, FHL2, PMAIP1, BTG2, CDKN1A and TGFB2) for further analysis. Tamoxifen reverses the effect of E2 on the expression of all selected genes, suggesting that they are direct targets of estrogen receptor. Furthermore, DAC treatment reactivates the expression of all selected genes in a dose-dependent manner. Promoter CpG island methylation status analysis revealed that only the promoters of BTG3 and FHL2 genes are methylated, with DAC inducing demethylation, suggesting DNA methylation directs repression of these genes in MCF-7 cells. In a further analysis of the potential interplay between estrogen signaling and DNA methylation, E2 treatment showed no effect on the methylation status of these promoters. Additionally, we show that the ERα recruitment occurs at the FHL2 promoter in an E2- and DAC-independent fashion. In conclusion, we identified a set of genes regulated by both estrogen signaling and DNA methylation. However, our data does not support a direct molecular interplay of mediators of estrogen and epigenetic signaling at promoters of regulated genes.
Biochemical and Biophysical Research Communications 08/2012; 426(1):26-32. · 2.48 Impact Factor
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Erik Arner,
Niklas Mejhert,
Agné Kulyté,
Piotr J Balwierz,
Mikhail Pachkov,
Mireille Cormont,
Silvia Lorente-Cebrián,
Anna Ehrlund,
Jurga Laurencikiene,
Per Hedén, Karin Dahlman-Wright,
Jean-François Tanti,
Yoshihide Hayashizaki,
Mikael Rydén,
Ingrid Dahlman,
Erik van Nimwegen,
Carsten O Daub,
Peter Arner
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ABSTRACT: In obesity, white adipose tissue (WAT) inflammation is linked to insulin resistance. Increased adipocyte chemokine (C-C motif) ligand 2 (CCL2) secretion may initiate adipose inflammation by attracting the migration of inflammatory cells into the tissue. Using an unbiased approach, we identified adipose microRNAs (miRNAs) that are dysregulated in human obesity and assessed their possible role in controlling CCL2 production. In subcutaneous WAT obtained from 56 subjects, 11 miRNAs were present in all subjects and downregulated in obesity. Of these, 10 affected adipocyte CCL2 secretion in vitro and for 2 miRNAs (miR-126 and miR-193b), regulatory circuits were defined. While miR-126 bound directly to the 3'-untranslated region of CCL2 mRNA, miR-193b regulated CCL2 production indirectly through a network of transcription factors, many of which have been identified in other inflammatory conditions. In addition, overexpression of miR-193b and miR-126 in a human monocyte/macrophage cell line attenuated CCL2 production. The levels of the two miRNAs in subcutaneous WAT were significantly associated with CCL2 secretion (miR-193b) and expression of integrin, α-X, an inflammatory macrophage marker (miR-193b and miR-126). Taken together, our data suggest that miRNAs may be important regulators of adipose inflammation through their effects on CCL2 release from human adipocytes and macrophages.
Diabetes 06/2012; 61(8):1986-93. · 8.29 Impact Factor
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ABSTRACT: Estrogen receptors (ERs), ERα and ERβ, mediate estrogen actions in a broad range of target tissues. With the introduction
of microarray techniques, a significant understanding has been gained regarding the interplay between the ERα and ERβ in breast
cancer cell lines. To gain a more comprehensive understanding of ERβ-dependent gene regulation independent of ERα, we performed
microarray analysis on HEK293/mock and HEK293/ERβ cells. A total of 332 genes was identified as ERβ-upregulated genes and
210 identified as ERβ-downregulated genes. ERβ-induced and ERβ-repressed genes were involved in cell–cell signaling, morphogenesis,
and cell proliferation. The ERβ repressive effect on genes related to proliferation was further studied by proliferation assays,
where ERβ expression resulted in a significant decrease in cell proliferation. To identify primary ERβ target genes, we examined
a number of ERβ-regulated genes using chromatin immunoprecipitation assays for regions bound by ERβ. Our results showed that
ERβ recruitment was significant to regions associated with 12 genes (IL1RAP, TMSB4X, COLEC12, ENPP2, KLRC1, RERG, RGS16, TNNT2,
CYR61, FER1L3, FAM108A1, and CYP4X1), suggesting that these genes are likely to be ERβ primary target genes. This study has
provided novel information on the gene regulatory function of ERβ independent of ERα and identified a number of ERβ primary
target genes. The results of Gene Ontology analysis and proliferation assays are consistent with an antiproliferative role
of ERβ independent of ERα.
KeywordsERβ-Microarray-HEK293-Target gene-Chromatin immunoprecipitation
Endocrine 04/2012; 36(2):224-232. · 1.42 Impact Factor
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ABSTRACT: The influence of estrogen signaling on infectious diseases is not fully known. Males seem to be more susceptible to infections than females. This has also been noted for the Scandinavian form of hemorrhagic fever with renal syndrome caused by Puumala hantavirus (PUUV). To investigate the differences in estrogen receptors in relation to sex and clinical severity, 20 patients (10 males, 10 females) with confirmed PUUV infection were studied. Real-time polymerase chain reaction was performed for analyzing mRNA expression of estrogen receptor-α (ERα), ERβ, and ERβ2 (ERβ cx) in peripheral blood mononuclear cells from patients and healthy age- and sex-matched blood donors. Blood chemistry and peripheral blood mononuclear cells sampling were performed during the acute and convalescent phases. None or very small amounts of ERβ were detected, and ERα and ERβ2 mRNA were elevated in the patient group. The samples from the males were correlated with ERβ2; the female samples, with ERα. Furthermore, the female and male samples are partly separated using multivariate statistic analysis (principal component analysis), supporting findings that clinical symptoms differ depending on sex.
Shock (Augusta, Ga.) 01/2012; 37(4):355-9. · 2.87 Impact Factor
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ABSTRACT: Metabolic disease and cancer are two of the leading causes of death worldwide. This review focuses on the potential increased relative risk for the development of cancer in a population with a rapidly increasing incidence of metabolic disturbances.
A large number of recent epidemiological and prospective studies link metabolic syndrome-associated diseases to an increased risk for development of, as well as mortality from, several types of cancer. In patients diagnosed with metabolic disorders, the incidence of gastrointestinal, glandular and reproductive tract cancers is significantly higher compared to the general population. In line with that, hyperglycemia has recently been shown to be an independent risk factor for overall cancer incidence.
Disorders connected to the metabolic syndrome have been shown to have profound impacts on the incidence and progression of cancer. Continued efforts to make lifestyle interventions, such as weight loss and increased physical activity in the general population, are clearly warranted as a contribution to efforts aimed at decreasing the development of and mortality from cancer. Progression in this field requires a better understanding of the underlying mechanisms behind the cancer-promoting effects associated with disturbed energy balance.
Current opinion in oncology 11/2011; 24(1):58-61. · 4.09 Impact Factor
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ABSTRACT: 4-Nonylphenol (4-NP), an estrogen mimicking compound is produced by biodegradation of alkylethoxylates. It is well established that 4-NP can affect the development of aquatic animals by disrupting the endocrine signals. Here we show for the first time in zebrafish that 4-NP does not only target the neuroendocrine system but also the notochord and the muscle. The notochord malformation was first evident as distortions at 24hourspostfertilization (hpf) which within 24h appeared as kinks and herniations. The notochord phenotype was accompanied by reduced motility and impaired swimming behavior. Whole-mount in situ hybridization using chordamesoderm markers and electron microscopic analysis showed failure in the notochord differentiation and disruption of the perinotochordal basement membrane. Late larval stages of 4-NP treated embryos displayed abnormal mineralization, vertebral curvature, fusion of vertebral bodies and abnormal extension of haemal arches. The muscle structure and the maximal active force in isolated muscle preparations were similar between 4-NP exposed and of control embryos, suggesting that 4-NP did not induce major changes in striated muscle function. However, repeated electrical stimulation (>40Hz) of the 4-NP exposed larvae revealed an impaired relaxation between stimuli, possibly reflecting an alteration in the relaxant mechanisms (e.g. in cellular Ca(2+) removal) which could explain the abnormal swimming pattern exhibited by 4-NP exposed larvae. Additionally, we demonstrate that the expression levels of the stress hormone, corticotropin releasing hormonewere elevated in the brain following 4-NP treatment. We also observed a significant decrease in the transcript levels of luteinizing hormone b at early larval stages. Collectively, our results show that 4-NP is able to disrupt the notochord morphogenesis, muscle function and the neuroendocrine system. These data suggest that 4-NP enduringly affects the embryonic development in zebrafish and that this compound might exert these deleterious effects through diverse signaling pathways.
Neurotoxicology and Teratology 11/2011; 33(6):752-64. · 2.98 Impact Factor
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10/2011; , ISBN: 978-953-307-341-5
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Hong Jiao,
Peter Arner,
Johan Hoffstedt,
David Brodin,
Beatrice Dubern,
Sébastien Czernichow,
Ferdinand van't Hooft,
Tomas Axelsson,
Oluf Pedersen,
Torben Hansen,
Thorkild I A Sørensen,
Johannes Hebebrand,
Juha Kere, Karin Dahlman-Wright,
Anders Hamsten,
Karine Clement,
Ingrid Dahlman
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ABSTRACT: Recent genome-wide association (GWA) analyses have identified common single nucleotide polymorphisms (SNPs) that are associated with obesity. However, the reported genetic variation in obesity explains only a minor fraction of the total genetic variation expected to be present in the population. Thus many genetic variants controlling obesity remain to be identified. The aim of this study was to use GWA followed by multiple stepwise validations to identify additional genes associated with obesity.
We performed a GWA analysis in 164 morbidly obese subjects (BMI:body mass index>40 kg/m2) and 163 Swedish subjects (>45 years) who had always been lean. The 700 SNPs displaying the strongest association with obesity in the GWA were analyzed in a second cohort comprising 460 morbidly obese subjects and 247 consistently lean Swedish adults. 23 SNPs remained significantly associated with obesity (nominal P<0.05) and were in a step-wise manner followed up in five additional cohorts from Sweden, France, and Germany together comprising 4214 obese and 5417 lean or population-based control individuals. Three samples, n=4133, were used to investigate the population-based associations with BMI. Gene expression in abdominal subcutaneous adipose tissue in relation to obesity was investigated for14 adults.
Potassium channel, calcium activated, large conductance, subfamily M, alpha member (KCNMA1) rs2116830*G and BDNF rs988712*G were associated with obesity in five of six investigated case-control cohorts. In meta-analysis of 4838 obese and 5827 control subjects we obtained genome-wide significant allelic association with obesity for KCNMA1 rs2116830*G with P=2.82×10(-10) and an odds ratio (OR) based on cases vs controls of 1.26 [95% C.I. 1.12-1.41] and for BDNF rs988712*G with P=5.2×10(-17) and an OR of 1.36 [95% C.I. 1.20-1.55]. KCNMA1 rs2116830*G was not associated with BMI in the population-based samples. Adipose tissue (P=0.0001) and fat cell (P=0.04) expression of KCNMA1 was increased in obesity.
We have identified KCNMA1 as a new susceptibility locus for obesity, and confirmed the association of the BDNF locus at the genome-wide significant level.
BMC Medical Genomics 06/2011; 4:51. · 3.69 Impact Factor
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ABSTRACT: The metabolic syndrome is a complex condition characterized by obesity, insulin resistance, decreased high-density lipoproteins, and hypertension associated with high risk of developing type 2 diabetes and cardiovascular disease. A major increase in the incidence of developing metabolic syndrome and related diseases is observed worldwide in association with a change toward a less active lifestyle and increased food consumption. Estrogen and the estrogen receptors (ERs) are well-known regulators of several aspects of metabolism, including glucose and lipid metabolism, and impaired estrogen signaling is associated with the development of metabolic diseases. This review will describe the key effects of estrogen signaling in metabolic and glucose sensing tissues, including the liver, pancreatic β cells, adipose tissue, and skeletal muscle. The impact on metabolic processes of impaired estrogen signaling and knock out of each ER subtype will also be discussed.
Journal of Endocrinology 04/2011; 212(1):3-12. · 3.55 Impact Factor
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Hong Jiao,
Peter Arner,
Suzanne L Dickson,
Hubert Vidal,
Niklas Mejhert,
Corneliu Henegar,
Magdalena Taube,
Caroline Hansson,
Anke Hinney,
Pilar Galan, [......],
Dominique Langin,
Martine Laville,
Cyrille Debard,
Tomas Axelsson,
Mikael Rydén,
Juha Kere, Karin Dahlman-Wright,
Anders Hamsten,
Karine Clement,
Ingrid Dahlman
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ABSTRACT: Previous studies suggest a role for fibroblast growth factor receptor 1 (FGFR1) in the regulation of energy balance.
Our objective was to investigate whether FGFR1 is an obesity gene by genetic association and functional studies.
The study was designed to genotype common FGFR1 single-nucleotide polymorphisms (SNP) in large cohorts, confirm significant results in additional cohorts, and measure FGFR1 expression in human adipose tissue and in rodent hypothalamus.
General community and referral centers for specialized care was the setting for the study.
We genotyped FGFR1 SNP in 2438 obese and 2115 lean adults and 985 obese and 532 population-based children. Results were confirmed in 928 obese and 2738 population-based adults and 487 obese and 441 lean children. Abdominal sc adipose tissue was investigated in 202 subjects. We also investigated diet-induced, obese fasting, and fed rats.
We analyzed the association between FGFR1 SNP and obesity. In secondary analyses, we related adipose FGFR1 expression to genotype, obesity, and degree of fat cell differentiation and related hypothalamic FGFR1 to energy balance.
FGFR1 rs7012413*T was nominally associated with obesity in all four cohorts; metaanalysis odds ratio = 1.17 (95% confidence interval = 1.10-1.25), and P = 1.8 × 10(-6), which was P = 7.0 × 10(-8) in the recessive model. rs7012413*T was associated with FGFR1 expression in adipose tissue (P < 0.0001). In this organ, but not in skeletal muscle, FGFR1 mRNA (P < 0.0001) and protein (P < 0.05) were increased in obesity. In rats, hypothalamic expression of FGFR1 declined after fasting (P < ]0.001) and increased after diet-induced obesity (P < 0.05).
FGFR1 is a novel obesity gene that may promote obesity by influencing adipose tissue and the hypothalamic control of appetite.
The Journal of clinical endocrinology and metabolism 03/2011; 96(6):E962-6. · 6.50 Impact Factor
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ABSTRACT: Estrogen signaling occurs widely among vertebrates and in some invertebrates. Estrogen action is mediated by estrogen receptors through the regulation of target gene expression. Estrogen mediated control of gene expression is a complex process including ligand-receptor interactions, receptor-DNA interactions and receptor-cofactor interactions. Recent technological advances allow global analysis of gene expression and protein-DNA interactions facilitating a description of estrogen controlled gene regulatory networks. This paper reviews the current knowledge of estrogen regulation of gene expression and subsequent gene regulatory networks with focus on studies using human cell lines and mouse models.
Molecular and Cellular Endocrinology 03/2011; 334(1-2):83-90. · 4.19 Impact Factor
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The EMBO Journal 01/2011; 30(13):2516-7. · 9.20 Impact Factor
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ABSTRACT: The metabolic syndrome constitutes a group of metabolic conditions that increase the risk of developing diseases, including cardiovascular disease (CVD) and type 2 diabetes (T2D). LXRα/β are regulators of lipogenesis, cholesterol/glucose homoeostasis and inflammatory pathways, processes that are intertwined with development of the metabolic syndrome. The employment of LXRs as pharmaceutical targets for treatment of various aspects of the metabolic syndrome has been promptly investigated but serious side effects, like hepatic steatosis, have hampered this process. Novel treatment regimes now focus on development of isoform-specific or tissue-specific LXR agonist/antagonist compounds to circumvent effects on lipid biosynthesis. Other strategies to explore the beneficial aspects of LXR activation include targeting co-factors or pathways that are modifying LXR activity.
Current Opinion in Pharmacology 12/2010; 10(6):692-7. · 6.86 Impact Factor
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ABSTRACT: Estrogens act by binding to and activating two estrogen receptors (ERs), ERα and ERβ. Transcriptional regulation by ERs is controlled by a complex array of factors such as ER-ligand binding, the DNA sequence bound by ERs, ER-interacting cofactors, and chromatin context. This minireview will provide an overview of the most recent advances in the identification of ERβ-regulated target gene networks and ERβ DNA-binding sites. We also highlight the recent work establishing new roles of ERβ signaling, including protective functions in the epithelial-mesenchymal transition and in atherosclerosis, as well as regulation of cell proliferation in the colon.
Journal of Biological Chemistry 10/2010; 285(51):39575-9. · 4.77 Impact Factor
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ABSTRACT: Estrogen signaling can occur through a nonclassical pathway involving the interaction of estrogen receptors (ER) with other transcription factors such as activator protein-1 (AP-1) and SP-1. However, there is little mechanistic understanding about this pathway, with conflicting results from in vitro investigations. In this study, we applied the ChIP-on-chip approach to identify ERbeta-binding sites on a genome-wide scale, identifying 1,457 high-confidence binding sites in ERbeta-overexpressing MCF7 breast cancer cells. Genes containing ERbeta-binding sites can be regulated by E2. Notably, approximately 60% of the genomic regions bound by ERbeta contained AP-1-like binding regions and estrogen response element-like sites, suggesting a functional association between AP-1 and ERbeta signaling. Chromatin immunoprecipitation (ChIP) analysis confirmed the association of AP-1, which is composed of the oncogenic transcription factors c-Fos and c-Jun, to ERbeta-bound DNA regions. Using a re-ChIP assay, we showed co-occupancy of ERbeta and AP-1 on chromatin. Short interfering RNA-mediated knockdown of c-Fos or c-Jun expression decreased ERbeta recruitment to chromatin, consistent with the role of AP-1 in mediating estrogen signaling in breast cancer cells. Additionally, ERalpha and ERbeta recruitment to AP-1/ERbeta target regions exhibited gene-dependent differences in response to antiestrogens. Together, our results broaden insights into ERbeta DNA-binding at the genomic level by revealing crosstalk with the AP-1 transcription factor.
Cancer Research 06/2010; 70(12):5174-83. · 7.86 Impact Factor
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ABSTRACT: Cell cycle regulatory pathways in breast cancer are incompletely described. Here, we report an important role in estrogen receptor alpha (ERalpha)-positive breast cancer cells for the protein kinase C1 (PKC1)-interacting protein RBCK1 in supporting cell cycle progression by driving transcription of ERalpha and cyclin B1. RBCK1-depleted cells exhibited increased accumulation in G(2)-M phase of the cell cycle, decreased proliferation, and reduced mRNA levels for ERalpha and its target genes cyclin D1 and c-myc. Chromatin immunoprecipitation revealed that ERalpha transcription is associated with RBCK1 recruitment to the ERalpha promoter, suggesting that transcriptional regulation is one mechanism by which RBCK1 affects ERalpha mRNA levels. G(2)-M phase arrest was mediated independently from reduced ERalpha levels, instead associated with transcriptional inhibition of the key G(2)-M regulator cyclin B1. In breast tumor samples, there was a positive correlation between levels of RBCK1, ERalpha, and cyclin B1 mRNA levels. Our findings suggest that RBCK1 regulates cell cycle progression and proliferation of ERalpha-positive breast cancer cells by supporting transcription of ERalpha and cyclin B1.
Cancer Research 02/2010; 70(3):1265-74. · 7.86 Impact Factor
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Paraskevi Moutsatsou,
Zoi Papoutsi,
Eva Kassi,
Nina Heldring,
Chunyan Zhao,
Anna Tsiapara,
Eleni Melliou,
George P Chrousos,
Ioanna Chinou,
Andrey Karshikoff,
Lennart Nilsson, Karin Dahlman-Wright
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ABSTRACT: Royal jelly (RJ) excreted by honeybees and used as a nutritional and medicinal agent has estrogen-like effects, yet the compounds mediating these effects remain unidentified. The possible effects of three RJ fatty acids (FAs) (10-hydroxy-2-decenoic-10H2DA, 3,10-dihydroxydecanoic-3,10DDA, sebacic acid-SA) on estrogen signaling was investigated in various cellular systems. In MCF-7 cells, FAs, in absence of estradiol (E(2)), modulated the estrogen receptor (ER) recruitment to the pS2 promoter and pS2 mRNA levels via only ERβ but not ERα, while in presence of E(2) FAs modulated both ERβ and ERα. Moreover, in presence of FAs, the E(2)-induced recruitment of the EAB1 co-activator peptide to ERα is masked and the E(2)-induced estrogen response element (ERE)-mediated transactivation is inhibited. In HeLa cells, in absence of E(2), FAs inhibited the ERE-mediated transactivation by ERβ but not ERα, while in presence of E(2), FAs inhibited ERE-activity by both ERβ and ERα. Molecular modeling revealed favorable binding of FAs to ERα at the co-activator-binding site, while binding assays showed that FAs did not bind to the ligand-binding pocket of ERα or ERβ. In KS483 osteoblasts, FAs, like E(2), induced mineralization via an ER-dependent way. Our data propose a possible molecular mechanism for the estrogenic activities of RJ's components which, although structurally entirely different from E(2), mediate estrogen signaling, at least in part, by modulating the recruitment of ERα, ERβ and co-activators to target genes.
PLoS ONE 01/2010; 5(12):e15594. · 4.09 Impact Factor
