title: Differential ERα-mediated rapid estrogenic actions of ginsenoside Rg1 and estren in human breast cancer MCF-7 cells.
abstract: Recent studies indicated that both estren and Rg1 appear to be able to activate mitogen-activated protein kinase (MAPK) pathway in estrogen responsive cells. Rg1 could lead to MAPK activation through ligand-independent activation of estrogen receptor (ER), while estren could activate the Src-MAPK pathway in an ERE-independent manner. Thus, it is important to understand the mechanistic insights on the difference in transcriptional activation between estren and Rg1. The present study also addressed the differential abilities of Rg1 and estren in terms of the ability to activate ER and the ability to induce ER translocation in MCF-7 cells. Our data indicated that Rg1 could increase pS2 gene expression, and could recruit the co-activator steroid receptor co-activator-1 (SRC-1) to the pS2 promoter. Rg1 could also induce ERα nuclear translocation as well as ERα phosphorylation at Ser118 principally in the cytoplasm in MCF-7 cells. We deduced that estren induced ERE-dependent transcriptional activity and activated ERα at Ser118 occurred in the nucleus of MCF-7 cells. However, it was found to decrease pS2 gene expression and failed to induce the recruitment of SRC-1 to the pS2 promoter in MCF-7 cells. Our results suggest that the abilities of Rg1 and estren to regulate pS2 gene expression, to recruit co-activators as well as to induce sub-cellular distribution of ERα are dramatically different.
authors: Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Special Administrative Region.
authors: Quan-Gui
authors: QG
authors: Gao
authors: Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Special Administrative Region.
authors: Hoi-Yi
authors: HY
authors: Chan
authors: Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Special Administrative Region.
authors: Cornelia Wing-Yin
authors: CW
authors: Man
authors: Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Special Administrative Region; State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen 518057, China. Electronic address: bcmswong@polyu.edu.hk.
authors: Man-Sau
authors: MS
authors: Wong
mesh_terms: D001943:Breast Neoplasms; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology; D004963:Estrenes / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D020218:Response Elements; D014158:Transcription, Genetic; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C468666:4-estren-3,17-diol; C506487:ESR1 protein, human; D004963:Estrenes; D047628:Estrogen Receptor alpha; D004967:Estrogens; D036145:Ginsenosides; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D004958:Estradiol; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C035054:ginsenoside Rg1
keywords: 17β-Estradiol; Estren; Estrogen receptor; Ginsenoside Rg1; MCF-7 cells