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Various SERMs mediate differential gene expression in SH‐SY5Y
Author(s) -
Barnette Damien,
Fonville Breanna,
McCauley Delauren,
Victoria Miller,
Gerald Tonya
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.219
Subject(s) - selective estrogen receptor modulator , estrogen receptor , estrogen receptor beta , estrogen receptor alpha , tamoxifen , dopamine receptor d2 , dopamine , medicine , dopamine receptor , endocrinology , receptor , chemistry , biology , pharmacology , cancer , breast cancer
Selective estrogen receptor modulators (SERMs) are a class of drugs that mimic or counteract estrogen effects and acts on the estrogen receptor sub‐types, ER alpha and/or ER beta. A characteristic that distinguishes SERMs from receptor agonists and antagonists is that their action is different for various tissues, (e.g.brain). (Ohmichi et al. , 2005). Therefore, this set of experiments was to determine D2‐like and ER‐subtype gene expression in the human neuroblastoma cell line, SH‐SY5Y with the GlaxoSmithKline SERM, GSK653580A (GSK SERM); a gift from Dave Jones of GlaxoSmithKline, RTP, NC), estrogen (E2 or Tamoxifen after 24 hour treatment. These receptor sets are associated with various brain pathologies. Isolated total RNA was analyzed via real‐time polymerase chain reaction. Preliminary results suggest significant differential changes mediated via GSK‐SERM‐dependent increases in ER beta gene expression, but minimal dose‐dependent response of D2 dopamine receptor, D4 dopamine receptor or ER alpha receptor subtypes. At 10 − 9 M, E2 represses gene expression for D 2 dopamine, D 4 dopamine and both ER sub‐types while Tamoxifen causes significant changes in the gene expression of the D 2 dopamine receptor sub‐type but no significant changes occurred for D 4 dopamine, ER alpha or ER beta receptors. D3 dopamine receptor was undetected in treated or untreated cells. Changes in expression could translate into modulation of other downstream events. NCCU College of Science and Technology SEED Grant, Duke‐NCCU STEM Partnership Program , and NSF ‐ HRD0411529 (NCCU ITTSTEM Program)