• Molecules and Cells
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• 제26권5호
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• pp.454-458
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• 2008

Sex steroid hormone receptors play a central role in modulating telomerase activity, especially in cancer cells. However, information on the regulation of steroid hormone receptors and their distinct functions on telomerase activity within the mesenchymal stem cell are largely unavailable due to low telomerase activity in the cell. In this study, the effects of estrogen ($E_2$) treatment and function of estrogen receptor alpha ($ER{\alpha}$) and estrogen receptor beta ($ER{\beta}$) on telomerase activity were investigated in human mesenchymal stem cells (hMSCs). Telomerase activity and mRNA expression of the catalytic subunit of telomerase (hTERT) were upregulated by treatment of the cells with $E_2$. The protein concentration of $ER{\alpha}$ was also increased by $E_2$ treatment, and enhancement of $ER{\alpha}$ accumulation in the nucleus was clearly detected with immunocytochemistry. When $ER{\alpha}$ expression was reduced by siRNA transfection into hMSCs, the effect of $E_2$ on the induction of hTERT expression and telomerase activity was diminished. In contrast, the transient overexpression of $ER{\alpha}$ increased the effect of $E_2$ on the expression of hTERT mRNA. These findings indicate that the activation of hTERT expression and telomerase activity by $E_2$ in hMSCs depends on $ER{\alpha}$, but not on $ER{\beta}$.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.292.2-293
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• 2002

Pyrethroids are one of the most commonly used insecticides in worldwide. but it remains unclear whether pyrethroid compounds possess endocrine disrupting activity or not. T47D cells, an estrogen receptor positive human breast cancer cell line. is known to induce alkaline phosphatase (AlkP) only in response to progestins. Because the action of estrogen may be changed by the action of progestins (Kraus et al. 1995), it is important to examine the potential to produce progestin-mediated effects for determining endocrine disrupting activity of chemicals(LiLorenzo et al. 1991). (omitted)

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.112-112
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• 2001

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxin that activates the aryl hydrocarbon receptor (AhR) and disrupts multiple endocrine signaling pathways by enhancing ligand metabolism, altering hormone synthesis, down regulating receptor levels, and interfering with gene transcription. And TCDD-mediated gene transactivation via the AhR has been shown to be dependent upon estrogen receptor (ER) expression in human breast cancer cells. In the present study, we have examined the effect of natural estrogen, phytoestrognes and environmental estrogens on the regulation of CYP1A1 gene expression in MCF-7 human breast cancer cell line. that ER and AhR are co-expressed. pCYP1A1 -luc reporter gene was transiently transfected into MCF-7 cells. These cells were treated with various chemicals and then luciferase assay was carried out. 17be1a-estradiol significantly inhibited TCDD stimulated luciferase activity dose dependently and this inhibition was partially recovered by concomitant treatment of tamoxifen. 17beta-estradiol metabolites, 2-hydroxyestradiol and 16alpha-estriol resulted in less potent inhibitory effect than estradiol and synthetic estrogen, diethylstilbestrol (DES) showed no effect on CYP1A1 gene expression. This study demonstrated that estrogen down-regulated TCDD stimulated CYP1A1 expression via ER mediation. And we have found out that several flavonoids such as genistein, kaempferol, daidzein, naringenin, and alkylphenols such as nonylphenol, 4-octylphenol and resveratrol also inhibited TCDD induced CYP1A1 expression like estrogen.

• International Journal of Oral Biology
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• 제32권2호
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• pp.67-73
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• 2007

Periodontitis is a chronic infectious disease that leads to periodontal destruction, and is one of the major causes of tooth loss in humans. The osteoclast differentiation factor (ODF), which is also known as the receptor activator of the NF-kB ligand (RANKL), is a surface-associated ligand on bone marrow stromal cells and osteoblasts. RANKL activates its cognate receptor, RANK, on osteoclast progenitor cells, which leads to the differentiation of mononucleated precursor cells. Osteoprotegerin (OPG) is a decoy receptor that is released from stromal cells and osteoblasts to inhibit the interaction between RANKL and RANK. Although the precise mechanism of bone loss in periodontitis is unknown, the differentiation and activation of osteoclasts by OPG-ODF-RANK signaling might play the role in periodontal bone destruction. The relationship between the concentration of sex hormones and the expression of ODF and OPG was examined by treating human gingival fibroblasts and periodontal ligament cells with the normal serum concentration of estrogen or progesterone during menstruation or at menopause. The ODF/OPG relative ratio was elevated at the concentration observed during ovulation in human gingival fibroblasts and at the concentration observed between ovulation and menstruation in periodontal ligament cells treated with estrogen. However, the ratio was <1 at all concentrations in both cells treated with progesterone. In the case of menopause simulated by estrogen depletion, the ratio was <1 in human gingival fibroblasts but >1 in periodontal ligament cells.

• BMB Reports
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• 제39권4호
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• pp.448-451
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• 2006

Chemopreventive and cytotoxic effect of genistein against human breast cancer cell lines was investigated. Genistein inhibited cell proliferation in estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) human breast carcinoma cell lines. Cytochrome P450 (CYP) 1A1-mediated ethoxyresorufin O-deethylase (EROD) activity was inhibited by genistein in a concentrationdependent manner. Genistein significantly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cyclooxy-genase-2 activity and protein expression at the concentrations of 10 (p < 0.05), 25 (p < 0.05) and 50 mM (p < 0.01). In addition, ornithine decarboxylase (ODC) activity was reduced to 53.8 % of the control after 6 h treatment with 50 mM genistein in MCF-7 breast cancer cells. These results suggest that genistein could be of therapeutic value in preventing human breast cancer.

• International Journal of Oral Biology
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• 제36권2호
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• pp.103-108
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• 2011

Measurement of estrogen concentration in bio-samples are very important for differential diagnosis of various disease or evaluation of health status. However, it is difficult to collect immediate data of estrogen concentration because they are measured by radioimmunoassay or chromatography which need time- and cost-consuming sample pre-treatment. This study was performed for development of new estrogen biosensor employing taste principles, and for evaluation of cross reactivity between various steroid hormones. Gene sequence of ligand binding domain of ${\alpha}$-human estrogen receptor (amino acid 302-553; hER-LBD) was cloned from human breast cancer cell line. The proteins of hER-LBD were produced by T7-E.coli expression system, and isolated by chromatography. hER-LBD were coated on the gold plated quartz crystal (AT-cut 9MHz), and resonance frequencies were measured by universal frequency counter. Estradiol, progesterone, testosterone, and aldosterone were used for cross reactivity of the hER-LBD. We also monitored influences of pH change in resonance frequency. The resonance frequencies of hER-LBD coated quartz crystal were decreased during increase of estrogen concentration from $15 \;{\mu}g/mL$ to $50\;{\mu}g/mL$. However, similar steroid hormones, progesterone and aldosterone, did not elicit the change in resonance frequency. Testosterone evoke weak change in resonance frequency. The new estrogen biosensor was more sensitive in pH 7.2 than in pH 7.6. These results suggest that hER-LBD coated quartz crystal biosensor is a probable estrogen biosensor.

• BMB Reports
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• 제29권4호
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• pp.314-320
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• 1996

The effects of non-cytotoxic concentrations of tamoxifen, verapamil, and trifluoperazine on doxorubicin cytotoxicity in five human breast cancer cell lines were studied. A non-cytotoxic concentration of tamoxifen resulted in enhanced doxorubicin cytotoxicity in HTB-123, HTB-26, and MCF-7. In these three cell lines, a combination of tamoxifen with verapamil resulted in even more increased doxorubicin cytotoxicity. Addition of verapamil or trifluoperazine alone did not influence the doxorubicin cytotoxicity significantly. Only in HTB-19 did coincubation with verapamil increase the doxorubicin cytotoxicity. In HTB-123, combination of tamoxifen with trifluoperazine increased the doxorubicin cytotoxicity significantly. In the cell lines where co-incubation with tamoxifen increased doxorubicin sensitivity, high estrogen receptor expression was detected. However, HTB-20, where tamoxifen did not enhance doxorubicin action, was also estrogen receptor positive. None of the cell lines had multidrug resistance related drug efflux and drug retention was not increased by the treatment with tamoxifen and verapamil. Cell cycle traverses were not altered by incubation with tamoxifen, verapamil or combinations thereof. These observatlons suggest mechanism of non-cytotoxic concentrations of tamoxifen and verapamil on doxorubicin cytotoxicity may involve one or more other cellular processes besides those of interference of estrogen binding to its receptor, cell cycle perturbation, or drug efflux blocking.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2161-2166
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• 2015

Estrogen receptors (ERs) are steroid receptors located in the cytoplasm and on the nuclear membrane. The sequence similarities of human $ER{\alpha}$, mouse $ER{\alpha}$, rat $ER{\alpha}$, dog $ER{\alpha}$, and cat $ER{\alpha}$ are above 90%, but structures of $ER{\alpha}$ may different among species. Estrogen can be agonist and antagonist depending on its target organs. This hormone play roles in several diseases including breast cancer. There are variety of the relative binding affinity (RBA) of ER and estrogen species in comparison to $17{\beta}-estradiol$ (E2), which is a natural ligand of both $ER{\alpha}$ and $ER{\beta}$. The RBA of the estrogen species are as following: diethyl stilbestrol (DES) > hexestrol > dienestrol > $17{\beta}-estradiol$ (E2) > 17- estradiol > moxestrol > estriol (E3) >4-OH estradiol > estrone-3-sulfate. Estrogen mimetic drugs, selective estrogen receptor modulators (SERMs), have been used as hormonal therapy for ER positive breast cancer and postmenopausal osteoporosis. In the postgenomic era, in silico models have become effective tools for modern drug discovery. These provide three dimensional structures of many transmembrane receptors and enzymes, which are important targets of de novo drug development. The estimated inhibition constants (Ki) from computational model have been used as a screening procedure before in vitro and in vivo studies.

• Natural Product Sciences
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• 제25권1호
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• pp.28-33
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• 2019

A popular approach for the study of estrogen receptor ${\alpha}$ inhibition is to investigate the protein-protein interaction between the estrogen receptor (ER) and the coactivator surface. In our study, we investigated phytochemicals from Rubus coreanus that were able to disrupt $ER{\alpha}$ and coactivator interaction with an $ER{\alpha}$ antagonist. The E-screen assay and molecular docking analysis were performed to evaluate the effects of the estrogenic activity of R. coreanus extract and its constituents on the MCF-7 human breast cancer cell line. At $100{\mu}g/mL$, R. coreanus extract significantly stimulated cell proliferation ($574.57{\pm}8.56%$). Sanguiin H6, which was isolated from R. coreanus, demonstrated the strongest affinity for the $ER{\alpha}$ coactivator-binding site in molecular docking analysis, with a binding energy of -250.149. The initial results of the study indicated that sanguiin H6 contributed to the estrogenic activity of R. coreanus through the activation of the $ER{\alpha}$ coactivator-binding site.

• 생약학회지
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• 제37권1호통권144호
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• pp.21-27
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• 2006

Yeast based estrogenicity assay is the simplest and useful for the assay and the discovery of novel estrogenic substances in natural specimens, The estrogen receptor(ER) modulation activity of 50% EtOH extracts of 101 traditional medicinal herbs was assessed using a recombinant yeast assay system with both a human estrogen receptor expression plasmid and a receptor plasmid. Among them, 14 species proved to be active. Pureariae Flos (flower of Puerraria thunbergiana BENTH.) had the highest estrogenic relative potency$(7.75{\times}10^{-3})$ $(EC_{50}=9.39\;{\mu}g/ml)$. The $EC_{50}$ value of $17{\beta}-estradiol$ used as the positive control was $0.073\;{\mu}g/ml)$ (Relative Potency=1.00). There results demonstrated that some of the traditional medical herb may be useful in the therapy of estrogen replacement.