Document Detail


Up-regulation of PI3K/Akt signaling by 17beta-estradiol through activation of estrogen receptor-alpha, but not estrogen receptor-beta, and stimulates cell growth in breast cancer cells.
MedLine Citation:
PMID:  16169518     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Estrogen stimulates cell proliferation in breast cancer. The biological effects of estrogen are mediated through two intracellular receptors, estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta). However, the role of ERs in the proliferative action of estrogen is not well established. Recently, it has been known that ER activates phosphatidylinositol-3-OH kinase (PI3K) through binding with the p85 regulatory subunit of PI3K. Therefore, possible mechanisms may include ER-mediated phosphoinositide metabolism with subsequent formation of phosphatidylinositol-3,4,5-trisphosphate (PIP(3)), which is generated from phosphatidylinositol 4,5-bisphosphate via PI3K activation. The present study demonstrates that 17beta-estradiol (E2) up-regulates PI3K in an ERalpha-dependent manner, but not ERbeta, and stimulates cell growth in breast cancer cells. In order to study this phenomenon, we have treated ERalpha-positive MCF-7 cells and ERalpha-negative MDA-MB-231 cells with 10nM E2. Treatment of MCF-7 cells with E2 resulted in a marked increase in PI3K (p85) expression, which paralleled an increase in phospho-Akt (Ser-473) and PIP(3) level. These observations also correlated with an increased activity to E2-induced cell proliferation. However, these effects of E2 on breast cancer cells were not observed in the MDA-MB-231 cell line, indicating that the E2-mediated up-regulation of PI3K/Akt pathway is ERalpha-dependent. These results suggest that estrogen activates PI3K/Akt signaling through ERalpha-dependent mechanism in MCF-7 cells.
Authors:
Young-Rae Lee; Jinny Park; Hong-Nu Yu; Jong-Suk Kim; Hyun Jo Youn; Sung Hoo Jung
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  336     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-10-03     Completed Date:  2005-12-12     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1221-6     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Center for Healthcare Technology Development, Chonbuk National University Medical School, Jeonju, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / biosynthesis,  physiology*
Breast Neoplasms / metabolism,  pathology*
Cell Line, Tumor
Cell Proliferation
Estradiol / pharmacology,  physiology*
Estrogen Receptor alpha / agonists*
Estrogen Receptor beta / agonists*
Female
Humans
Mammary Glands, Human / metabolism,  pathology
Phosphatidylinositol Phosphates / metabolism
Phosphorylation
Proto-Oncogene Proteins c-akt / biosynthesis,  physiology*
Signal Transduction
Up-Regulation
Chemical
Reg. No./Substance:
0/Estrogen Receptor alpha; 0/Estrogen Receptor beta; 0/Phosphatidylinositol Phosphates; 0/phosphatidylinositol 3,4,5-triphosphate; 50-28-2/Estradiol; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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