Molecular Mechanism of Action of Selective Estrogen Receptor Modulator in Target Tissues

Ohmichi, Masahide; Tasaka, Keiichi; Kurachi, Hirohisa; Murata, Yuji

doi:10.1507/endocrj.52.161

Cited by 22 publications

(12 citation statements)

References 65 publications

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“…Unlike 17β‐estradiol (E 2 ), several synthetic ER ligands, such as tamoxifen, raloxifene or other selective oestrogen receptor modulators, exhibit a distinct binding affinity to ERα and ERβ ( Plouffe, 2000 ; Gluck and Maricic, 2003 ; Albertazzi and Sharma, 2005 ). It has been suggested that the molecular mechanisms involved in the tissue‐selective action of these substances include ER subtype‐specific effects ( Diel, 2002 ; Ohmichi et al , 2005 ). Moreover, the effects of some phytoestrogens, compounds of plant origin with affinity to the ER, are also proposed to be mediated via ER subtype specific mechanisms ( Fitzpatrick, 2003 ).…”

Section: Introductionmentioning

confidence: 99%

Analysis of the effects of oestrogen receptor α (ERα)‐ and ERβ‐selective ligands given in combination to ovariectomized rats

Hertrampf

Seibel

Laudenbach

et al. 2008

British J Pharmacology

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Background and purpose: Studies with oestrogen receptora (ERa)-and ERb-selective compounds have already shown that the effects of 17b-estradiol (E 2 ) on body weight, movement drive and bone-protection are mediated via ERa. This study was based on the hypothesis that activation of ERb may antagonize ERa-mediated effects and designed to investigate potential effects of ERa/ERb heterodimers. Experimental approach: Ovariectomized (OVX) female Wistar rats were treated with combinations of the ERa-specific agonist 16a-LE2 (ALPHA; 1 and 10 mg kg À1 d À1 ), the ERb-specific agonist 8b-VE2 (BETA; 100 mg kg À1 d À1 ), the phytoestrogen, genistein (10 mg kg À1 d À1 ) and with the anti-oestrogen compound, ICI 182,780 (3 mg kg À1 d À1 ) for three weeks. The combined effects of the substances on body weight increase, tibial bone mineral density (BMD) and the influence on running wheel activity (RWA) were investigated. Key results: OVX-induced body weight increase was reduced by co-administration of genistein and BETA. Co-application of BETA or genistein with ALPHA had no effect on ALPHA-mediated bone-protection. The RWA of OVX animals was significantly reduced by treatment with genistein but stimulated by application of ALPHA. The stimulatory effect of ALPHA on RWA could be antagonized by co-treatment with the pure antioestrogen ICI 182,780 but also by co-administration of genistein or BETA. Conclusions and implications:Our results indicate that activation of ERb may modulate ERa-mediated physiological effects in vivo. The observation that substances with selective affinity for ERb are able to antagonize distinct physiological functions, like RWA, may be of great relevance to the pharmaceutical use of such drugs.

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Section: Introductionmentioning

confidence: 99%

Analysis of the effects of oestrogen receptor α (ERα)‐ and ERβ‐selective ligands given in combination to ovariectomized rats

Hertrampf

Seibel

Laudenbach

et al. 2008

British J Pharmacology

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“…tumour growth inhibitory effects upon binding rather than estrogenic, growth promoting responses. While the first-generation antiestrogens like tamoxifen 22a had severe unwanted side-effects including neo-carcinogenity upon long-term exposure, modern selective estrogen receptor modulators (SERM) usually provide balanced estrogenic-antiestrogenic profiles [63]. Raloxifen 23 for example exhibits a desired agonistic (i.e.…”

Section: Conjugates With Selective Estrogen Receptor Modulators (Serm)mentioning

confidence: 99%

Metallodrug Conjugates with Steroids and Selective Estrogen Receptor Modulators (SERM)

Biersack

Schobert

2009

CMC

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An overview of conjugates of coordination complexes and organometallic complexes of Pt, Ru, Fe, Re, lanthanoids and other metals with natural and synthetic estrogens and antiestrogens targeting the nuclear estrogen receptors is provided. These conjugates are used as targeted cytotoxic agents or - if radiolabeled - as imaging probes for the detection of estrogen receptor-rich tissues such as hormone-dependent tumours. They are assessed with respect to their estrogen receptor binding affinities, potential synergistic cytotoxic effects in cancer cells and their specificity for tumour over non-malignant cells and tissues. The mechanisms of their modes of action are discussed. Pertinent literature is covered up to 2008.

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“…Recent studies suggests that c-myc is a direct transcription factor for the hTERT gene [174]. The role of several genes as telomerase modulators is now known, [175][176][177]. This is significant because hTERT levels provide the rate-limiting link to telomerase activity [33,161].…”

Section: Damd17-02-1-0581mentioning

confidence: 99%

Analysis of Breast Cell-Lineage Response Differences to Taxol Using a Novel Co-Culture System

Gollahon¹,

Collie²

2005

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. Email: ]auren.gollahon@ttu.edu REPORT DATE PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERTexas Tech University Lubbock, TX 79409 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTESOriginal contains colored plates: ALL DTIC reproductions will be in black and white.14. ABSTRACT We have established a new co-culture system in which human mammary epithelial cells (HMEC) and human mammary tumor cells (HMT) are physically grown together. We hypothesized that cells in co-culture (CC) would generate gene expression profiles different from homogeneous cell populations. In this study, cells were incubated with blue or red CellTracker Dyes and co-cultured. Our novel capture system allowed cells to be co-cultured and then quickly separated while maintaining -90% viability. Using deconvolution microscopy, co-cultured HMEC were observed to form focal, gland-like structures surrounded by TTUderived from an invasive ductal carcinoma. Using a differential trypsinization technique, cell populations were rapidly separated to perform RNA extractions performed (<2 h) in order to obtain expression profiles from still viable cells. RT2 profiler PCR Array (SuperArray) RT-PCR was utilized to analyze differential gene expression between parent cell lines and cells co-cultured. We observed that in co-culture HMEC become more cancerous compared to homogenous parent HMEC and CC -TTUexhibit gene expression profiles considered to be less cancerous that that of parent HMT. Replated CC HMEC have both gene expression profiles of CC HMEC and parent HMEC, but were more similar to CC HMEC. Replated TTU showed similar results. DAMD1 7-02-1-0581 SUBJECTGollahon, Lauren, S. Gollahon, Lauren, S. INTRODUCTION:The subject of this research is investigating whether different normal cell types, isolated from primary breast tissue 1) respond differently in co-cul...

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Molecular Mechanism of Action of Selective Estrogen Receptor Modulator in Target Tissues

Cited by 22 publications

References 65 publications

Analysis of the effects of oestrogen receptor α (ERα)‐ and ERβ‐selective ligands given in combination to ovariectomized rats

Analysis of the effects of oestrogen receptor α (ERα)‐ and ERβ‐selective ligands given in combination to ovariectomized rats

Metallodrug Conjugates with Steroids and Selective Estrogen Receptor Modulators (SERM)

Analysis of Breast Cell-Lineage Response Differences to Taxol Using a Novel Co-Culture System

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