Document Detail


Phosphoinositide 3-kinase inhibitor LY294002 but not serum withdrawal suppresses proliferation of murine embryonic stem cells.
MedLine Citation:
PMID:  17321171     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mouse embryonic stem (mES) cells have short duration of their cell cycle and are capable of proliferating in the absence of growth factors. To find out which signaling pathways contribute to the regulation of the mES cell cycle, we used pharmacological inhibitors of MAP and PI3 kinase cascades. The MAP kinase inhibitors as well as serum withdrawal did not affect mES cell cycle distribution, whereas the inhibitor of PI3K activity, LY294002, induced accumulation of cells in G(1) phase followed by apoptotic cell death. Serum withdrawal also causes apoptosis, but it does not change the content and activity of cell cycle regulators. In contrast, in mES cells treated with LY294002, the activities of Cdk2 and E2F were significantly decreased. Interestingly, LY294002had a much stronger effect on cell cycle distribution in low serum conditions, implying that serum can promote G(1)-->S transition of mES cells by a LY294002-resistant mechanism. Thus, proliferation of mES cells is maintained by at least two separate mechanisms: a LY294002-sensitive pathway, which is active even in the absence of serum, and LY294002-resistant, but serum-dependent, pathway.
Authors:
Maria S Lianguzova; Ilia A Chuykin; Alfred Nordheim; Valery A Pospelov
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-01-21
Journal Detail:
Title:  Cell biology international     Volume:  31     ISSN:  1065-6995     ISO Abbreviation:  Cell Biol. Int.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-04-02     Completed Date:  2007-06-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9307129     Medline TA:  Cell Biol Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  330-7     Citation Subset:  IM    
Affiliation:
Institute of Cytology, RAS, St. Petersburg 194064, Russian Federation.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / antagonists & inhibitors*
Animals
Cell Cycle / drug effects
Cell Proliferation / drug effects*
Cells, Cultured / drug effects
Chromones / pharmacology*
Culture Media, Serum-Free*
E2F Transcription Factors / metabolism
Embryonic Stem Cells / drug effects*
Enzyme Inhibitors / pharmacology*
Mice
Morpholines / pharmacology*
Chemical
Reg. No./Substance:
0/Chromones; 0/Culture Media, Serum-Free; 0/E2F Transcription Factors; 0/Enzyme Inhibitors; 0/Morpholines; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase

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