• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5047-5052
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• 2012

Introduction: Breast cancer is the most common malignancy of women in Kashmir. This study was conducted with the objective of assessing hormone receptor positivity and its correlation with age at diagnosis, tumor size, histological grade and lymph node metastasis. Materials and Methods: 132 newly diagnosed cases of invasive breast cancer diagnosed at the Department of Pathology, SKIMS, Srinagar, J&K, were included after excluding biopsies, in-situ lesions and recurrence cases. Results: Mean age of the patients was 48.2 years, 59.1% being ${\leq}50$ years of age. Mean duration of symptoms was 6.32 months. Most lesions (65.1%) were 2-5 cm and 16.7% were ${\geq}5.0$ cm in greatest dimension. The predominant (80.3%) morphology was IDC-NOS. The majority of the cases presented as grade II (52.1%) lesions and lymph node involvement was present in 65.2%. ER and PR were positive in 66.3% and 63.4% cases, respectively, increasing with rising age. High grade lesions and larger size tumors were more likely to be ER and PR negative. No correlation was found between ER/PR status and lymph node metastasis. Conclusions: ER and PR expression in breast cancers in the current study was found to be higher than studies done in India/Asia but lower than studies conducted in the West, even on Indian/Asian immigrants. Markedly lower receptor expression in Indian/Asian studies is likely due to preanalytic variables, thresholds for positivity, and interpretation criteria. American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer are strongly advocated for standardization of receptor evaluation and for clinical management of breast cancer patients to provide best therapeutic options.

• The Korean Journal of Cytopathology
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• v.5 no.1
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• pp.10-14
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• 1994

The expression of sex steroid hormone receptors by neoplastic cells is an important predictor of response to hormone therapy. Thus, the selection of treatment modality is often based on the identification of receptors in tumor tissue. Various monoclonal antibodies of high specificity are now available for analyzing the estrogen receptor (ER). With these antibodies, biochemical enzyme immunoassay and immunohistochemistry using histologic sections have been used for ER analysis. We used fine needle aspirates from 15 human primary breast carinomas for the analysis of ERs. The semiquantitative receptor values obtained in cytologic specimens were correlated well with those from histologic specimens. The results of ER in fine needle aspirates were concordant with ER in histologic specimens(r=0.94). Only three cases showed a little difference in staining intensity and proportion of positive cells. Our results showed a good correlation between the receptor values determined in cytologic smears and those determined in tissue sections. It is suggested that measurement of the ER in cytologic smears may be a reliable technique which can be performed on aspiration cytologic samples.

• Environmental Mutagens and Carcinogens
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• v.22 no.3
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• pp.175-182
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• 2002

Endocrine disruptors (EDs) are the chemicals that affect endocrine systems through activation or inhibition of steroid hormone response. It is necessary to have a good system to evaluate rapidly and accurately endocrine-disrupting activities of suspected chemicals and their degradation products. The key targets of EDs are nuclear hormone receptors, which bind to steroid hormones and regulate their gene transcription. We constructed a co-expression system of Gal4p DNA binding domain (DBD)- ligand binding domain of human estrogen receptor $\alpha$ or $\beta$, and Gal4p transactivation domain (TAD)-co-activator AIB-1, SRC-1 or TIF-2 in Saccharomyces cerevisiae with a chromosome-integrated lacZ reporter gene under the control of CYC1 promoter and Gal4p binding site (GAL4 upstream activating sequence, GAL4$_{UAS}$). Expression of this reporter gene was dependent on the presence of estrogen or EDs in the culture medium. We found that the two-hybrid system with combination of the hER$\beta$ LBD and co-activator SRC-1 was most effective in the xenoestrogen-dependent induction of reporter activity. The extent of transcriptional activation by those chemicals correlated with their estrogenic activities measured by other assay systems, indicating that this assay system is efficient and reliable for measuring estrogenic activity. The data in this research demonstrated that the yeast detection system using steroid hormone receptor and co-activator is a useful tool for identifying chemicals that interact with steroid receptors.s.

• Clinical and Experimental Reproductive Medicine
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• v.16 no.2
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• pp.131-138
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• 1989

The present study was designed to develop a new method for the determination of estrogen receptor in porcine uterus using frozen sections. Cryostat sections were incubated with $^3H$-estradiol($^3H$-$E_2$) in the presence or absence of diethylstilbestrol(DES) and the radioactivity of 3H-E2 bound to estrogen receptor(ER) was detected. The level of specific estrogen receptor was determined by Scatchard analysis. The highest ratio of specific binding against total binding was achieved in 3 sec. tions(5mm x 5mm) which was corresponded to lOO${\mu}$/ml protein concentration. Optimal binding was obtained during incubation with $^3H$-$E_2$ for 30 minutes at 23$^{\circ}C$ after treatment of sections with acetone for 20 seconds. Three time-washing of sections was proved to be appropriate for the removal of unbound 3H-E2. 200-fold molar excess of DES was substituted for the binding of $^3H$-$E_2$ to ER sufficiently(binding efficiency of 54.8%). ER was saturated with 4nM of $^3H$-$E_2$ and its dissociation constant was 0.1nM. ER assay using frozen sections(Histological radioreceptor assay, HRRA) was significantly correlated with radioreceptor assay for estradiol(RRA, 0.976 , p

• Molecules and Cells
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• v.26 no.3
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• pp.285-290
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• 2008

Estrogen-induced proliferation in estrogen receptor (ER)-positive breast cancer cells is primarily mediated through two distinct intracellular receptors, $ER{\alpha}$ and $ER{\beta}$. Although tumor necrosis factor alpha ($TNF{\alpha}$) and $E2/ER{\alpha}$ are known to exert opposing effects on cell proliferation in MCF-7 cells, the mechanism by which $TNF{\alpha}$ antagonizes $E2/ER{\alpha}$-mediated cell proliferation is not well understood. The present study suggests that reduced cell survival in response to $TNF{\alpha}$ treatment in MCF-7 cells may be associated with the down-regulation of $ER{\alpha}$ protein. The decrease in $ER{\alpha}$ protein level was accompanied by an inhibition of $ER{\alpha}$ gene transcription. Cell viability was decreased synergistically by the combined treatment with $ER{\alpha}$-siRNA and $TNF{\alpha}$. Furthermore, pretreatment of cells with the PI3-kinase (PI3K)/ Akt inhibitor, LY294002, markedly enhanced $TNF{\alpha}$-induced down-regulation of the $ER{\alpha}$ protein, suggesting that the PI3K/Akt pathway might be involved in control of the $ER{\alpha}$ level. Moreover, down-regulation of $ER{\alpha}$ by $TNF{\alpha}$ was not inhibited in cells that were pretreated with the proteasome inhibitors, MG132 and MG152, which suggests that proteasome-dependent proteolysis does not significantly influence $TNF{\alpha}$-induced down-regulation of $ER{\alpha}$ protein. In contrast, the effect of the PI3K/Akt inhibitor on $ER{\alpha}$ was blocked in cells that were treated with LY294002 in the presence of the proteasome inhibitors. Collectively, our findings show that the $TNF{\alpha}$ may partly regulate the growth of MCF-7 breast cancer cells through the down-regulation of $ER{\alpha}$ expression, which is primarily mediated by a PI3K/Akt signaling.

• Journal of Nutrition and Health
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• v.38 no.7
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• pp.512-520
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• 2005

Phytoestrogens, especially Yak-kong or soybean-derived isoflavones have been traditionally used as a supplement of estrogen for preventing postmenopausal osteoporosis in oriental folk medicine. In a previous study, we demonstrated that as Yak-kong and soybean increased MG-63 human osteoblastic cell proliferation, the expression of estrogen receptor $\alpha\;and\;beta\;(ER\;\alpha:\;ER\;\beta$) both were increased. However, the increased level of ER $\alpha$ is much higher than that of ER$\beta$. To determine whether the altered level of ER $\alpha$ expression affects Yak-kong or soybean induced MG-63 cell proliferation, we established cell lines stably expressing either ER $\alpha$ or antisense ER $\alpha$ RNAs. Increased expression of ER a in MG- 63 cells (ER $\alpha$-MG63) enhanced Yak-kong or soybean induced proliferation which paralleled with the enhanced expression of IGF-I. Inhibition of ER $\alpha$ expression by antisense $ER\;\alpha\;RNAs\;(As-ER\;\alpha-MG63$) caused these cells to insensitize Yak- kong or soybean induced proliferation and IGF-I expression. Furthermore, the comparable effects between Yak-kong and the combined treatment of genistein and daidzein at $0.5\;{\times}\;10^{-8}M$, which is a concentration of these two isoflavones similar to Yak-kong at 0.001 mg/ml, on cell proliferation and IGF-I expression in $ER\;\alpha-MG63\;or\;As-ER\;\alpha-MG63$ cells demonstrate that ER $\alpha$ plays an important, active role in MG-63 cell proliferation induced by phytoestrogens, especially Yak-kong or soybean derived isoflavones.

• Development and Reproduction
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• v.13 no.4
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• pp.249-256
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• 2009

The estrogen receptor-related receptors (ERRs) are a group of nuclear receptor superfamily of transcription factors. ERRs and estrogen receptors (ERs) have overlapping affinities for coactivators and DNA binding sites, but differ markedly in ligand binding and activation. The three mammalian ERR genes have been implicated in diverse physiological processes ranging from placental development to maintenance of bone density, whereas the molecular diversity, function, and regulation of ERRs in non-mammalian species are not well understood. In the present study, to investigate the involvement of ERR in transcription and embryogenesis in marine invertebrates, a cDNA encoding ERR (SnERR) was cloned from the gonad in Strongylocentrotus nudus, by polymerase chain reaction (PCR). The amino acid sequence of SnERR showed high homology with that of S. purpuratus (91%). A phylogenetic tree clearly showed that SnERR is a member of the ERR family and clustered in echinodermata group as supported by a high bootstrap value. We examined gene expression of SnERR during embryonic development of S. nudus using real-time PCR. During the embryonic development, the mRNA of ERR was significantly high levels in early development stages (4~64 cell) and larval stages. The SnERR slightly activated transcription through the classical estrogen response elements (EREs) in the presence of genistein. In addition, peroxisome proliferator-activated receptor $\gamma$ coactivator (PGC)-$1\alpha$ knwon as a coactivator of ERR enhanced the snERR-mediated transactivation, suggesting that the PGC-$1\alpha$ is a coactivator of SnERR.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2002.10a
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• pp.164-164
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• 2002

에스트로젠을 처리한 송사리의 간으로부터 choriogenin vitellogenin estrogen receptor의 발현량을 전사수준에서 Real-time을 사용하여 정량.비교하였다. 시험어종으로는 부화 후 5개월 이상된 성숙한 수컷 송사리(Oryzias latipes)를(체중 약 250mg/마리)를 사용하여 17$\beta$-estradiol(25ppt, 50ppt, 100ppt)에 24시간 노출시켰다. Fluorescence dye는 choriogenin vitellogenin estrogen receptor의 경우 FAM (6-carboxyfluorescein)을 사용하였으며, $\beta$-actin의 경우는 VIC를 사용하였다. 프로브에 사용하는 quencher dye는 TAMRA(6-carboxy-N',N',N',N'-tetramethyl rhodamine)을 사용하였다. Internal control로 사용된 $\beta$-actin은 17$\beta$-estradiol의 농도에 상관 없이 0~10pM 범위에서 일정하게 발현됨을 보여주었다. vitellogenin choriogenin L 및 choriogenin H는 17$\beta$-estradiol의 농도에 의존하여 발현이 증가되는 용량-반응양상(Dose-dependent)을 나타내었다. 반면, estrogen receptor는 모든 처리군에서 $10^{-2}$pM 정도로 발혐됨에 따라 본 시험농도의 17$\beta$-estradiol에 의해서는 거의 유도발현이 되지 않음을 보여주었다. choriogenin L, choriogenin H, vitellogenin I 및 estrogen receptor 발현감수성을 비교한 결과, 25ppt 및 50ppt의 17$\beta$-esoadiol 농도에서는 ChgL > ChgH > VTG I >ER의 순으로 감수성이 높았으며, 100ppt 노출에서는 ChgL > VTG I > Chg H > ER의 순으로 감수성이 높게 나타났다. 결론적으로 choriogenin이 에스트로젠물질에 의한 가장 민감한 생체지표임을 알 수 있었다.

• Toxicological Research
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• v.27 no.2
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• pp.85-93
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• 2011

Selective estrogen receptor modulators (SERMs) are synthetic molecules which bind to estrogen receptors (ER) and can modulate its transcriptional capabilities in different ways in diverse estrogen target tissues. Tamoxifen, the prototypical SERM, is extensively used for targeted therapy of ER positive breast cancers. Unfortunately, the use of tamoxifen is associated with acquired resistance and some undesirable side effects. This study investigated the availability of the conventional SERMs on the TAM-resistance breast cancer cells. SERMs showed more effectiveness in MCF-7 cells than tamoxifen resistant cells, except toremifene and ospemifene. Especially, toremifene was more efficacious in tamoxifen resistant cells than MCF-7. Ospemifene had similar cytotoxic activity on the two types of breast cancers. The other SERMs used in this experiment didn't inhibit efficiently the proliferation of tamoxifen resistant cells. These results support the possibility to usage of toremifene on tamoxifen resistant cancer. The effectiveness by toremifene on tamoxifen resistant cells might be different pathways from the apoptosis and the autophagy. Further study should be needed to elucidate the underlying mechanism of effect of toremifene on tamoxifen resistant cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4049-4052
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• 2013

Resistance to chemotherapy treatment, which may lead to limited efficacy of systemic therapy in breast cancer patients, is multifactorial. Among the mechanisms of resistance to chemotherapy treatment, there are those closely related to estrogen receptor ${\alpha}$, P-glycoprotein, multidrug resistance-related protein, glutathione S-transferase pi and topoisomerase-II. $ER{\alpha}$ is ligand-activated transcription factor that regulates gene expression and plays a critical role in endocrine signaling. In previous preclinical and clinical studies, positive $ER{\alpha}$ expression in breast cancer cells was correlated with decreased sensitivity to chemotherapy. This article reviews current knowledge on the predictive value of $ER{\alpha}$ with regard to response to chemotherapy. Better understanding of its role may facilitate patient selection of therapeutic regimens and lead to optimal clinical outcomes.