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  • 1
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    Molecular determinants for the tissue specificity of SERMs (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-03-30
    Description: Selective estrogen receptor modulators (SERMs) mimic estrogen action in certain tissues while opposing it in others. The therapeutic effectiveness of SERMs such as tamoxifen and raloxifene in breast cancer depends on their antiestrogenic activity. In the uterus, however, tamoxifen is estrogenic. Here, we show that both tamoxifen and raloxifene induce the recruitment of corepressors to target gene promoters in mammary cells. In endometrial cells, tamoxifen, but not raloxifene, acts like estrogen by stimulating the recruitment of coactivators to a subset of genes. The estrogen-like activity of tamoxifen in the uterus requires a high level of steroid receptor coactivator 1 (SRC-1) expression. Thus cell type- and promoter-specific differences in coregulator recruitment determine the cellular response to SERMs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shang, Yongfeng -- Brown, Myles -- CA57374/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Mar 29;295(5564):2465-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Adult Oncology, Dana-Farber Cancer Institute, 44 Binney Street, and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11923541" target="_blank"〉PubMed〈/a〉
    Keywords: Breast/*drug effects/metabolism ; Breast Neoplasms/genetics/metabolism ; Cell Cycle ; DNA-Binding Proteins/metabolism ; Endometrial Neoplasms/genetics/metabolism ; Endometrium/*drug effects/metabolism ; Estradiol/pharmacology ; Female ; Gene Expression Regulation/drug effects ; Gene Silencing ; Genes, myc ; Histone Acetyltransferases ; Histone Deacetylases/metabolism ; Humans ; Insulin-Like Growth Factor I/genetics ; Nuclear Receptor Coactivator 1 ; Organ Specificity ; Promoter Regions, Genetic ; Raloxifene Hydrochloride/metabolism/*pharmacology ; Receptors, Estrogen/chemistry/metabolism ; Repressor Proteins/metabolism ; Response Elements ; Selective Estrogen Receptor Modulators/metabolism/*pharmacology ; Tamoxifen/metabolism/*pharmacology ; Transcription Factors/genetics/*metabolism ; Transcription, Genetic ; Tumor Cells, Cultured
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Alleviating neuropathic pain hypersensitivity by inhibiting PKMzeta in the anterior cingulate cortex (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-12-04
    Description: Synaptic plasticity is a key mechanism for chronic pain. It occurs at different levels of the central nervous system, including spinal cord and cortex. Studies have mainly focused on signaling proteins that trigger these plastic changes, whereas few have addressed the maintenance of plastic changes related to chronic pain. We found that protein kinase M zeta (PKMzeta) maintains pain-induced persistent changes in the mouse anterior cingulate cortex (ACC). Peripheral nerve injury caused activation of PKMzeta in the ACC, and inhibiting PKMzeta by a selective inhibitor, zeta-pseudosubstrate inhibitory peptide (ZIP), erased synaptic potentiation. Microinjection of ZIP into the ACC blocked behavioral sensitization. These results suggest that PKMzeta in the ACC acts to maintain neuropathic pain. PKMzeta could thus be a new therapeutic target for treating chronic pain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Xiang-Yao -- Ko, Hyoung-Gon -- Chen, Tao -- Descalzi, Giannina -- Koga, Kohei -- Wang, Hansen -- Kim, Susan S -- Shang, Yuze -- Kwak, Chuljung -- Park, Soo-Won -- Shim, Jaehoon -- Lee, Kyungmin -- Collingridge, Graham L -- Kaang, Bong-Kiun -- Zhuo, Min -- CIHR66975/Canadian Institutes of Health Research/Canada -- CIHR84256/Canadian Institutes of Health Research/Canada -- G0601813/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2010 Dec 3;330(6009):1400-4. doi: 10.1126/science.1191792.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Faculty of Medicine, Center for the Study of Pain, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21127255" target="_blank"〉PubMed〈/a〉
    Keywords: Adenylyl Cyclases/genetics/metabolism ; Analgesics/administration & dosage/pharmacology ; Animals ; Enzyme Inhibitors/administration & dosage/*pharmacology ; Excitatory Postsynaptic Potentials/drug effects ; Gyrus Cinguli/*enzymology/physiology ; Long-Term Potentiation ; Male ; Memory/drug effects ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neuralgia/*drug therapy/*enzymology ; Patch-Clamp Techniques ; Peptides/administration & dosage/*pharmacology ; Peroneal Nerve/injuries ; Phosphorylation ; Protein Kinase C/*antagonists & inhibitors/*metabolism ; Receptors, AMPA/metabolism ; Sensory Receptor Cells/physiology ; Somatosensory Cortex/physiology ; Synapses/physiology ; Synaptic Transmission
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
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