DOCSLIB.ORG

Breast Cancer Res 7

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Breast Cancer Res 7 Available online http://breast-cancer-research.com/content/7/5/R753 ResearchVol 7 No 5 article Open Access Phosphorylation of estrogen receptor α serine 167 is predictive of response to endocrine therapy and increases postrelapse survival in metastatic breast cancer Hiroko Yamashita1, Mariko Nishio2, Shunzo Kobayashi3, Yoshiaki Ando1, Hiroshi Sugiura1, Zhenhuan Zhang2, Maho Hamaguchi1, Keiko Mita1, Yoshitaka Fujii1 and Hirotaka Iwase2 1Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan 2Oncology and Endocrinology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan 3Josai Municipal Hospital of Nagoya, Nagoya, Japan Corresponding author: Hiroko Yamashita, [email protected] Received: 29 Jan 2005 Revisions requested: 15 Apr 2005 Revisions received: 12 Jun 2005 Accepted: 28 Jun 2005 Published: 27 Jul 2005 Breast Cancer Research 2005, 7:R753-R764 (DOI 10.1186/bcr1285) This article is online at: http://breast-cancer-research.com/content/7/5/R753 © 2005 Yamashita et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/ 2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Introduction Endocrine therapy is the most important treatment Results Phosphorylation of ER-α Ser118, but not Ser167, was option for women with hormone-receptor-positive breast positively associated with overexpression of HER2, and HER2- cancer. The potential mechanisms for endocrine resistance positive tumors showed resistance to endocrine therapy. The involve estrogen receptor (ER)-coregulatory proteins and present study has shown for the first time that phosphorylation crosstalk between ER and other growth factor signaling of ER-α Ser167, but not Ser118, and expression of PRA and networks. However, the factors and pathways responsible for PRB, as well as ER-α and PR in primary breast tumors are endocrine resistance are still poorly identified. predictive of response to endocrine therapy, whereas expression of ER-β1 and ER-βcx/β2 did not affect response to Methods Using immunohistochemical techniques, we focused the therapy. In addition, patients with either high on the expression and phosphorylation of hormone receptors phosphorylation of ER-α Ser167, or high expression of ER-α, themselves and examined the phosphorylation of ER-α Ser118 PR, PRA, or PRB had a significantly longer survival after relapse. and ER-α Ser167 and the expression of ER-α, ER-β1, ER-βcx/ β2, progesterone receptor (PR), PRA, and PRB in the primary Conclusion These data suggest that phosphorylation of ER-α breast carcinomas of 75 patients with metastatic breast cancer Ser167 is helpful in selecting patients who may benefit from who received first-line treatment with endocrine therapy after endocrine therapy and is a prognostic marker in metastatic relapse. breast cancer. Introduction latory proteins and crosstalk between the ER pathway and The development and progression of breast cancer are influ- other growth factor signaling networks [1,2]. An understand- enced by steroid hormones, particularly estrogen, via their ing of the molecular mechanisms that modulate the activity of interaction with specific target receptors. Endocrine therapy the estrogen signaling network has enabled new ways of over- has become the most important treatment option for women coming endocrine resistance to be developed. with estrogen receptor (ER)-positive breast cancer. Neverthe- less, many breast cancer patients with tumors expressing high ER-α is phosphorylated on multiple amino acid residues [3]. levels of ER are unresponsive to endocrine therapy, and all Serines 104, 106, 118, and 167 are all located within the acti- patients with advanced disease eventually develop resistance vation function (AF)1 region of ER-α, and their phosphoryla- to the therapy. The potential mechanisms behind either this tion provides the important mechanism that regulates AF1 intrinsic or acquired endocrine resistance involve ER-coregu- activity [4,5]. In response to estradiol binding, human ER-α is β AF = action function; DMEM = Dulbecco's modified essential medium; E2 = 17 -estradiol; EGF = epidermal growth factor; ER = estrogen receptor; IHC = immunohistochemistry/immunohistochemical; MAPK = mitogen-activated protein kinase; PR = progesterone receptor. R753 Breast Cancer Research Vol 7 No 5 Yamashita et al. phosphorylated mainly on Ser118 and to a lesser extent on described previously [17]. T47D cells (ATCC) were grown in Ser104 and Ser106 [4]. Although some authors have also RPMI-1640 supplemented with 10% fetal calf serum, 2 mM L- reported that Ser167 is a major estradiol-induced phosphor- glutamine, and penicillin–streptomycin (50 IU/ml and 50 mg/ ylation site [5,6], this response to estradiol has not been uni- ml, respectively), at 37°C with 5% CO2. Six microliters of versally observed [4,7]. Interestingly, in response to the FuGENE6 transfection reagent (Roche Molecular Biochemi- activation of the mitogen-activated protein kinase (MAPK) cals, Indianapolis, IN, USA), 3 µg of an expression vector for pathway, phosphorylation occurs on Ser118 and Ser167 human ER-α cDNA (pSG5/puromycine hERα, full length, [8,9]. However, the role of phosphorylation of Ser118 and kindly provided by Pierre Chambon, Strasbourg, France) were Ser167 of ER-α in human breast cancer has not been used for transfection into COS-7 cells as described previously investigated. [18]. After transfection, cells were starved in serum-free DMEM without phenol red for 20 hours. ER-β and its splicing isoforms are widely expressed in both normal and malignant breast tissue [10]. Although several Immunoblotting groups have reported results regarding the possible function Cells were treated in the absence or presence of 17β-estra- β of ER- , and its potential as a prognostic or predictive factor diol (E2) (10 nM, Sigma-Aldrich Co, St Louis, MO, USA) and/ in breast cancer, the data remain inconclusive and are often or epidermal growth factor (EGF) (100 ng/ml, human recom- contradictory [11,12]. ER-βcx (also called ER-β2), a splice var- binant EGF, Sigma-Aldrich) for 30 min, pelleted by centrifuga- iant of ER-β, is considered to be a dominant repressor of ER- tion and solubilized in lysis buffer containing 10 mM Tris-HCl, α; it is identical to ER-β1 (wild-type ER-β) except that the last pH 7.6, 5 mM EDTA, 50 mM NaCl, 30 mM sodium pyrophos- exon, 8, is replaced by 26 amino acid residues [13]. The role phate, 50 mM sodium fluoride, 1 mM sodium orthovanadate, of ER-β and its isoforms, especially with respect to the 1% Triton X-100, 1 mM phenylmethylsulfonylfluoride (PMSF), response of breast cancer to endocrine therapy, has also not 5 µg/ml aprotinin, 1 µg/ml pepstatin A, and 2 µg/ml leupeptin, been elucidated. as described previously [19]. Equal amounts of total protein from whole-cell lysates were prepared and used for SDS– Progesterone receptors (PRs) occur as two isoforms, PRA PAGE. Immunoblotting was performed as described previ- and PRB, transcribed from two distinct promoters on a single ously [18] using polyvinylidene difluoride (PVDF) membranes gene. PRA, but not PRB, lacks the 164 amino acid N-terminal (Invitrogen, Carlsbad, CA, USA; Catalogue no. LC2002), and residues that contain AF3, and this is the cause of their func- polyclonal antibody against ER-α (H-184, Santa Cruz Biotech- tional differences [14]. In the mammary gland, the overexpres- nology, Santa Cruz, CA, USA) (1:200 dilution), polyclonal rab- sion of PRA relative to PRB results in extensive epithelial cell bit antiphospho-ER-α (Ser118) antibody (Cell Signaling hyperplasia, excessive ductal branching, and a disorganized Technology, Beverly, MA, USA) (1:500 dilution), polyclonal basement membrane, all features associated with neoplasia rabbit antiphospho-ER-α (Ser167) antibody (Cell Signaling) [15]. In contrast, the overexpression of PRB leads to prema- (1:500 dilution) as primary antibodies and horseradish-peroxi- ture arrest of ductal growth and inadequate lobuloalveolar dif- dase-conjugated goat antibodies to rabbit IgG as secondary ferentiation [16]. However, little is known about the unique antibodies in conjunction with enhanced chemiluminescence roles of the two PR isoforms in breast cancer. substrate mixture (SuperSignal WestPico Chemiluminescent Substrate, Pierce, Rockford, IL, USA) in accordance with the In this study, we focused on the expression and phosphoryla- manufacturer's instructions. Phospho-ER-α Ser118 antibody tion of the hormone receptors themselves and, using immuno- detects ER-α only when the receptor is phosphorylated at histochemistry (IHC), examined the phosphorylation of ER-α Ser118, and not at Ser106 or Ser167; and phospho-ER-α Ser118 and Ser167 and the expression of ER-α, ER-β1, ER- Ser167 antibody detects ER-α only when the receptor is βcx/β2, PR, PRA, and PRB in primary breast tumor specimens phosphorylated at Ser167, and not at Ser106 or Ser118, by from 75 patients with metastatic breast cancer who received immunoblotting, as described by Chen and colleagues [20]. first-line treatment with endocrine therapy on relapse. Our results show that patients with primary breast tumors in which Generation of specific antibodies for ER-β proteins there is either high phosphorylation of ER-α Ser167 or high To detect specific ER-β1 and ER-βcx/β2 proteins, rabbit poly- expression of ER-α, PR,
Load more

Recommended publications
  • Progestins Inhibit the Growth of MDA-MB-231 Cells Transfected with Progesterone Receptor Complementary DNA1
    Vol. 5, 395–403, February 1999 Clinical Cancer Research 395 Progestins Inhibit the Growth of MDA-MB-231 Cells Transfected with Progesterone Receptor Complementary DNA1 Valerie C-L. Lin,2 Eng Hen Ng, Swee Eng Aw, INTRODUCTION Michelle G-K. Tan, Esther H-L. Ng, The involvement of progesterone in the growth and devel- Vivian S-W. Chan, and Gay Hui Ho opment of breast cancer has been increasingly recognized in recent years. However, the roles of progesterone in the growth Departments of Clinical Research, Ministry of Health (V. C-L. L., regulation of breast cancer are still controversial. Progestins are S. E. A., M. G-K. T., V. S-W. C.), and General Surgery, Singapore General Hospital (E. H. N., E. H-L. N., G. H. H.), Republic of found to stimulate growth, have no effect, or inhibit growth in Singapore 169608 breast cancer cells (1–13). The conflicting findings affect clin- ical decision as to whether progestins or antiprogestins would be more appropriate endocrine therapies for PgR3-positive breast ABSTRACT cancer. Although progestins such as MPA and megestrol acetate Because progesterone exerts its effects mainly via estro- are often effectively used in the treatment of breast cancer gen-dependent progesterone receptor (PgR), the expression (14–16), a number of reports advocate that antiprogestins may of progesterone’s effects may be overshadowed by the prim- be new powerful tools for treating hormone-dependent breast ing effect of estrogen. PgR expression vectors were trans- cancer (17–19). fected into estrogen receptor (ER)-a and PgR-negative The reasons for the inconsistency in reported effects of breast cancer cells MDA-MB-231; thus the functions of progestins are not clear, but the involvement of estrogen and ER progesterone could be studied independent of estrogens and in the demonstrated effects of progestins is an important factor ERs.
    [Show full text]
  • Transcriptional and Progesterone Receptor Binding Profiles of the Human
    bioRxiv preprint doi: https://doi.org/10.1101/680181; this version posted June 23, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Transcriptional and Progesterone Receptor Binding Profiles of the Human 2 Endometrium Reveal Important Pathways and Regulators in the Epithelium During 3 the Window of Implantation 4 5 Ru-pin Alicia Chi1, Tianyuan Wang2, Nyssa Adams3, San-pin Wu1, Steven L. Young4, 6 Thomas E. Spencer5,6, and Francesco DeMayo1 7 8 1 Reproductive and Developmental Biology Laboratory, National Institute of 9 Environmental Health Sciences, Research Triangle Park, North Carolina, USA 10 2 Integrative Bioinformatics Support Group, National Institute of Environmental Health 11 Sciences, Research Triangle Park, North Carolina, USA 12 3 Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor 13 College of Medicine, Houston, Texas, USA 14 4 Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, 15 Chapel Hill, North Carolina, USA 16 5 Division of Animal Sciences and 6Department of Obstetrics, Gynecology and Women’s 17 Health, University of Missouri, Columbia, Missouri, USA 18 19 1 bioRxiv preprint doi: https://doi.org/10.1101/680181; this version posted June 23, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license.
    [Show full text]
  • Progesterone Receptor Isoform B Regulates the Oxtr-Plcl2-Trpc3 Pathway to Suppress Uterine Contractility
    Progesterone receptor isoform B regulates the Oxtr-Plcl2-Trpc3 pathway to suppress uterine contractility Mary C. Peaveya,1, San-Pin Wub,1, Rong Lib, Jian Liub, Olivia M. Emeryb, Tianyuan Wangc, Lecong Zhouc, Margeaux Wetendorfd, Chandra Yallampallie, William E. Gibbonse, John P. Lydond, and Francesco J. DeMayob,2 aDepartment of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC 27599; bReproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709; cIntegrative Bioinformatic Support Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709; dDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030; and eDepartment of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030 Edited by R. Michael Roberts, University of Missouri, Columbia, MO, and approved January 19, 2021 (received for review June 6, 2020) Uterine contractile dysfunction leads to pregnancy complications The “progesterone receptor isoform switch” concept was posited such as preterm birth and labor dystocia. In humans, it is hypoth- to explain the transition from a quiescent to a contractile myometrial esized that progesterone receptor isoform PGR-B promotes a re- phenotype in the presence of high levels of progesterone (10, 11, laxed state of the myometrium, and PGR-A facilitates uterine 26–30). Progesterone acts via the nuclear receptor isoforms, PGR-A contraction. This hypothesis was tested in vivo using transgenic and PGR-B, which are coexpressed at different levels throughout mouse models that overexpress PGR-A or PGR-B in smooth muscle pregnancy (31–35). Progesterone can transactivate different tran- cells. Elevated PGR-B abundance results in a marked increase in scriptional programs determined by the relative levels of PGR-A and gestational length compared to control mice (21.1 versus 19.1 d PGR-B isoforms in the myometrium (36–41).
    [Show full text]
  • The Novel Progesterone Receptor
    0013-7227/99/$03.00/0 Vol. 140, No. 3 Endocrinology Printed in U.S.A. Copyright © 1999 by The Endocrine Society The Novel Progesterone Receptor Antagonists RTI 3021– 012 and RTI 3021–022 Exhibit Complex Glucocorticoid Receptor Antagonist Activities: Implications for the Development of Dissociated Antiprogestins* B. L. WAGNER†, G. POLLIO, P. GIANGRANDE‡, J. C. WEBSTER, M. BRESLIN, D. E. MAIS, C. E. COOK, W. V. VEDECKIS, J. A. CIDLOWSKI, AND D. P. MCDONNELL Department of Pharmacology and Cancer Biology (B.L.W., G.P., P.G., D.P.M.), Duke University Medical Center, Durham, North Carolina 27710; Molecular Endocrinology Group (J.C.W., J.A.C.), NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709; Department of Biochemistry and Molecular Biology (M.B., W.V.V.), Louisiana State University Medical School, New Orleans, Louisiana 70112; Ligand Pharmaceuticals, Inc. (D.E.M.), San Diego, California 92121; Research Triangle Institute (C.E.C.), Chemistry and Life Sciences, Research Triangle Park, North Carolina 27709 ABSTRACT by agonists for DNA response elements within target gene promoters. We have identified two novel compounds (RTI 3021–012 and RTI Accordingly, we observed that RU486, RTI 3021–012, and RTI 3021– 3021–022) that demonstrate similar affinities for human progeste- 022, when assayed for PR antagonist activity, accomplished both of rone receptor (PR) and display equivalent antiprogestenic activity. As these steps. Thus, all three compounds are “active antagonists” of PR with most antiprogestins, such as RU486, RTI 3021–012, and RTI function. When assayed on GR, however, RU486 alone functioned as 3021–022 also bind to the glucocorticoid receptor (GR) with high an active antagonist.
    [Show full text]
  • Culture Characters, Genetic Background, Estrogen/Progesterone Receptor Expression, and Tumorigenic Activities of Frequently Used
    Clinica Chimica Acta 489 (2019) 225–232 Contents lists available at ScienceDirect Clinica Chimica Acta journal homepage: www.elsevier.com/locate/cca Culture characters, genetic background, estrogen/progesterone receptor expression, and tumorigenic activities of frequently used sixteen T endometrial cancer cell lines Wanglei Qua,1, Yinling Zhaob,1, Xuan Wangc,1, Yaozhi Qid, Clare Zhoue, Ying Huaa, ⁎⁎ ⁎ Jianqing Houc, , Shi-Wen Jianga,f, a Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospitable of Wenzhou Medical University, Wenzhou 325027, China b Department of Gynecology, Taizhou People's Hospital, Taizhou 225300, Jiangsu, China c Department of Gynecology, Yantai Yuhuangding Hospital, Qingdao University School of Medicine, Yantai 264000, Shandong Province, China. d Department of Clinical Laboratory, Lianyungang Maternal and Child Health Hospital, Jiangsu 222005, China e Department of Obstetrics and Gynecology, Mayo Medical College, Rochester 55901, MN, USA f Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA 31404, USA ARTICLE INFO ABSTRACT Keywords: Background: This study aimed to determine the in vitro and in vivo properties of sixteen frequently used en- Endometrial cancer dometrial cancer (EC) cell lines, including the cell proliferation rate, morphology, hormone receptor expression Hormone receptor patterns, PTEN, hMLH1 expression, p53 mutation, karyotype, and tumorigenicity in mouse xenograt model. PTEN Methods: Twelve type I (AN3, ECC-1, EN, EN-1, EN-11, HEC-1A, HECe1B, Ishikawa, KLE, MFE-280, MFE-296, hMLH1 MFE-319) and four type II (ARK1, ARK2, HEC-155/180, SPEC-2) endometrial cancer cell lines were studied. Cell p53 mutation proliferation and morphology were determined using cell growth curves and light microscopy, respectively.
    [Show full text]
  • Molecular Identification and Characterization of a and B Forms of the Glucocorticoid Receptor
    Molecular Identification and Characterization of A and B Forms of the Glucocorticoid Receptor Matthew R. Yudt and John A. Cidlowski Laboratory of Signal Transduction National Institute of Environmental Health Sciences Downloaded from https://academic.oup.com/mend/article/15/7/1093/2748001 by guest on 27 September 2021 National Institutes of Health Research Triangle Park, North Carolina 27709 The human glucocorticoid receptor (hGR␣)isa responsive promoters reveal the shorter hGR-B to ligand-activated transcription factor that mediates be nearly twice as effective as the longer hGR-A the physiological effects of corticosteroid hor- species in gene transactivation, but not in transre- mones and is essential for life. Originally cloned in pression. (Molecular Endocrinology 15: 1093–1103, 1986, the transcriptionally active hGR␣ was re- 2001) ported to be a single protein species of 777 amino kDa). Biochemical 94 ؍ acids (molecular mass data, obtained using various mammalian tissues INTRODUCTION and cell lines, however, have consistently revealed an additional, slightly smaller, second hGR protein The glucocorticoid receptor (GR) mediates the physi- kDa) that is not recognized ological effects of corticosteroid hormones in species 91 ؍ molecular mass) by antibodies specific for the transcriptionally in- from fish to mammals. GR is a member of the nuclear active and dominant negative, non-hormone-bind- hormone receptor superfamily of ligand-activated ing hGR␤ isoform. We report here that when a transcription factors (1) and is essential for life (2). The single GR cDNA is transfected in COS-1 cells, or activity of the GR, as well as the progesterone (PR), transcribed and translated in vitro, two forms of androgen (AR), and mineralocorticoid receptors (MR) the receptor are observed, similar to those seen in is partially mediated through a palindromic response cells that contain endogenous GR.
    [Show full text]
  • Cloning of the Chicken Progesterone Receptor (Xgt11 Expression Screening/DNA Binding Domain/V-Erba/Progesterone Receptor Forms a and B) J
    Proc. Natl. Acad. Sci. USA Vol. 83, pp. 5424-5428, August 1986 Biochemistry Cloning of the chicken progesterone receptor (Xgt11 expression screening/DNA binding domain/v-erbA/progesterone receptor forms A and B) J. M. JELTSCH*, Z. KROZOWSKI*t, C. QUIRIN-STRICKER*, H. GRONEMEYERt, R. J. SIMPSON§, J. M. GARNIER*, A. KRUST*, F. JACOB*, AND P. CHAMBON* *Laboratoire de Gdndtique Moleculaire des Eucaryotes du Centre National de la Recherche Scientifique et Unit6 184 de Biologie Molcularie et de Genie G6ndtique de l'Institut National de la Santd et de la Recherche Mddicale, Institut de Chimie Biologique, Facult6 de M6decine, 67085 Strasbourg Cddex, France; MLudwig Institute for Cancer Research, Bern, Switzerland; and §Joint Protein Structure Laboratory, Ludwig Institute for Cancer Research, Melbourne Tumor Biology Branch/The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia Contributed by P. Chambon, April 10, 1986 ABSTRACT Monospecific antibodies directed against the ogous to these two domains are present in the product of the chicken progesterone receptor (PR) form B were used to screen v-erbA gene of the avian erythroblastosis virus (2, 7, 9). a randomly primed phage Xgtll cDNA expression library The chicken (ref. 10 and references therein) and the human prepared from size-fractionated chicken oviduct mRNA. Two (ref. 11 and references therein) progesterone receptors (PR) independent immunoreactive clones, AcPR1 and AcPR2, were exist in two forms, A and B, both of which bind progestins isolated. Antibodies selected from anti-PR form B antiserum on and DNA. In addition, a chicken PR form B antigen that does matrices of AcPR1 and AcPR2 fusion proteins detected two not bind the hormone has been described (12), and its cDNA proteins on electrophoretic immunoblots of crude and purified has been partially cloned (13).
    [Show full text]
  • Genome-Wide Crosstalk Between Steroid Receptors in Breast and Prostate Cancers
    28 9 Endocrine-Related V Paakinaho and J J Palvimo Steroid receptor crosstalk in 28:9 R231–R250 Cancer cancers REVIEW Genome-wide crosstalk between steroid receptors in breast and prostate cancers Ville Paakinaho and Jorma J Palvimo Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio, Finland Correspondence should be addressed to J J Palvimo: [email protected] Abstract Steroid receptors (SRs) constitute an important class of signal-dependent transcription Key Words factors (TFs). They regulate a variety of key biological processes and are crucial drug f androgen receptor targets in many disease states. In particular, estrogen (ER) and androgen receptors (AR) f estrogen receptor drive the development and progression of breast and prostate cancer, respectively. f glucocorticoid receptor Thus, they represent the main specific drug targets in these diseases. Recent evidence f progesterone receptor has suggested that the crosstalk between signal-dependent TFs is an important step f breast cancer in the reprogramming of chromatin sites; a signal-activated TF can expand or restrict f prostate cancer the chromatin binding of another TF. This crosstalk can rewire gene programs and thus f chromatin alter biological processes and influence the progression of disease. Lately, it has been f crosstalk postulated that there may be an important crosstalk between the AR and the ER with other SRs. Especially, progesterone (PR) and glucocorticoid receptor (GR) can reprogram chromatin binding of ER and gene programs in breast cancer cells. Furthermore, GR can take the place of AR in antiandrogen-resistant prostate cancer cells. Here, we review the current knowledge of the crosstalk between SRs in breast and prostate cancers.
    [Show full text]
  • Wednesday Scienti Ic Session Listings 639–830 Information at a Glance
    Chicago | October 17-21 Wednesday Scienti ic Session Listings 639–830 Information at a Glance Important Phone Numbers Annual Meeting Headquarters Office Mercy Hospital Key to Poster Floor by Themes Logistics and Programming 2525 S Michigan Avenue The poster floor begins with Theme A and ends Logistics Chicago, IL 60616 with Theme H. Refer to the poster floor map at McCormick Place: Hall A, (312) 791‑6700 (312) 567‑2000 the end of this booklet. Programming Physicians Immediate Care Theme McCormick Place: Hall A, (312) 791‑6705 811 S. State Street A Development Chicago, IL 60605 B Neural Excitability, Synapses, and Glia: Volunteer Leadership Lounge (312) 566‑9510 Cellular Mechanisms McCormick Place: S505A, (312) 791‑6735 Walgreens Pharmacy C Disorders of the Nervous System General Information Booths (closest to McCormick Place) D Sensory and Motor Systems McCormick Place: 3405 S. Martin Luther King Drive E Integrative Systems: Neuroendocrinology, Gate 3 Lobby, (312) 791‑6724 Chicago, IL 60616 Neuroimmunology and Homeostatic Challenge Hall A (312) 791‑6725 (312) 326‑4064 F Cognition and Behavior Press Offices Venues G Novel Methods and Technology Development Press Room McCormick Place H History, Teaching, Public Awareness, and McCormick Place: Room S501ABC 2301 S. Martin Luther King Drive Societal Impacts in Neuroscience (312) 791‑6730 Chicago, IL 60616 Exhibit Management Fairmont Chicago, Millennium Park Hotel Note: Theme H Posters will be located in Hall A McCormick Place: Hall A, (312) 791‑6740 200 N. Columbus Drive beginning at 1 p.m. on Saturday, Oct. 17, and will Chicago, IL 60601 remain posted until 5 p.m., Sunday, Oct.
    [Show full text]
  • Nuclear Progesterone Receptor Isoforms and Their Functions in the Female Reproductive Tract
    Polish Journal of Veterinary Sciences Vol. 14, No. 1 (2011), 149-158 DOI 10.2478/v10181-011-0024-9 Review Nuclear progesterone receptor isoforms and their functions in the female reproductive tract R. Rękawiecki, M.K. Kowalik, J. Kotwica Institute of Animal Reproduction and Food Research of Polish Academy of Science, Tuwima 10, 10-747 Olsztyn, Poland Abstract Progesterone (P4), which is produced by the corpus luteum (CL), creates proper conditions for the embryo implantation, its development, and ensures proper conditions for the duration of preg- nancy. Besides the non-genomic activity of P4 on target cells, its main physiological effect is caused through genomic action by the progesterone nuclear receptor (PGR). This nuclear progesterone receptor occurs in two specific isoforms, PGRA and PGRB. PGRA isoform acts as an inhibitor of transcriptional action of PGRB. The inactive receptor is connected with chaperone proteins and attachment of P4 causes disconnection of chaperones and unveiling of DNA binding domain (DBD). After receptor dimerization in the cells’ nucleus and interaction with hormone response element (HRE), the receptor coactivators are connected and transcription is initiated. The ratio of these isoforms changes during the estrous cycle and reflects the different levels of P4 effect on the repro- ductive system. Both isoforms, PGRA and PGRB, also show a different response to the P4 receptor antagonist activity. Connection of the antagonist to PGRA can block PGRB, but acting through the PGRB isoform, P4 receptor antagonist may undergo conversion to a strongly receptor agonist. A third isoform, PGRC, has also been revealed. This isoform is the shortest and does not have transcriptional activity.
    [Show full text]
  • Progesterone Receptor B As Prognostic Marker for Patient Survival
    Lenhard et al. BMC Cancer 2012, 12:553 http://www.biomedcentral.com/1471-2407/12/553 RESEARCH ARTICLE Open Access Steroid hormone receptor expression in ovarian cancer: progesterone receptor B as prognostic marker for patient survival Miriam Lenhard1*, Lennerová Tereza2, Sabine Heublein2, Nina Ditsch1, Isabelle Himsl1, Doris Mayr3, Klaus Friese1,2 and Udo Jeschke2 Abstract Background: There is partially conflicting evidence on the influence of the steroid hormones estrogen (E) and progesterone (P) on the development of ovarian cancer (OC). The aim of this study was to assess the expression of the receptor isoforms ER-α/-β and PR-A/-B in OC tissue and to analyze its impact on clinical and pathological features and patient outcome. Methods: 155 OC patients were included who had been diagnosed and treated between 1990 and 2002. Patient characteristics, histology and follow-up data were available. ER-α/-β and PR-A/-B expression were determined by immunohistochemistry. Results: OC tissue was positive for ER-α/-β in 31.4% and 60.1% and PR-A/-B in 36.2% and 33.8%, respectively. We identified significant differences in ER-β expression related to the histological subtype (p=0.041), stage (p=0.002) and grade (p=0.011) as well as PR-A and tumor stage (p=0.03). Interestingly, median receptor expression for ER-α and PR-A/-B was significantly higher in G1 vs. G2 OC. Kaplan Meier analysis revealed a good prognosis for ER-α positive (p=0.039) and PR-B positive (p<0.001) OC. In contrast, ER-β negative OC had a favorable outcome (p=0.049).
    [Show full text]
  • Transcription Factor I in Ovarian Epithelial Cancers and Normal Ovaries
    25-32 30/5/07 16:15 Page 25 ONCOLOGY REPORTS 18: 25-32, 2007 25 Analysis of the expression of estrogen receptor, progesterone receptor and chicken ovalbumin upstream promoter- transcription factor I in ovarian epithelial cancers and normal ovaries ROBÉRIO DE SOUSA DAMIÃO1, CELINA TIZUKO FUJIYAMA OSHIMA2, JOÃO NORBERTO STÁVALE2 and WAGNER JOSÉ GONÇALVES1 1Discipline of Gynecologic Oncology, Department of Gynecology, and 2Department of Pathology, Federal University of São Paulo, São Paulo, Brazil Received March 3, 2007; Accepted April 10, 2007 Abstract. Sex hormones are involved in the carcinogenesis survival or clinical prognostic variables. Multivariate analysis of some gynecologic cancers, and the status of their receptors revealed a residual tumor <1 cm as the most significant represents an indicator of prognosis and of the therapeutic clinical prognostic factor in group A (p=0.010, OR=4.14). response in breast and endometrial cancers. In the ovary, this These data support the importance of cytoreduction in the role is not clearly defined, with epithelial cancers being treatment of ovarian cancer, the role of steroid receptors in the poorly responsive to hormone therapy. COUP-TFI (chicken mechanism of carcinogenesis, and the need for selection of ovalbumin upstream promoter-transcription factor I) is an subgroups that may respond to hormone therapy. orphan nuclear receptor, which is expressed in various tissues and regulates the estrogen receptor (ER) by competition for Introduction DNA binding. To investigate the role of these receptors in ovarian carcinogenesis and their implications for cancer Ovarian cancer is the fourth most frequent cause of cancer prognosis, we evaluated the immunohistochemical expression death in Western countries (1).
    [Show full text]