Document Detail

Kinase-negative mutant epidermal growth factor receptor (EGFR) expression during embryonal stem cell differentiation favours EGFR-independent lineages.
MedLine Citation:
PMID:  8898244     Owner:  NLM     Status:  MEDLINE    
EGF receptors are expressed on most fetal and adult cells but their precise roles are not well known. We previously reported that, in P19 embryonal carcinoma cells, the expression of kinase-negative EGFR inhibits retinoic acid (RA)-induced differentiation to nervous tissue, suggesting that EGFR plays a role in differentiation (J.-X. Wu and E. D. Adamson (1993) Dev. Biol. 159, 208-222). Embryo stem (ES) cells differentiate into a wide range of tissue types after the removal of the cytokine LIF from the culture medium. We demonstrate here that the induction of some early markers of differentiation, tissue-type plasminogen activator (tPA), AFP and keratins 8 and 19 is inhibited, whilst brachyury and myosin are increased, in clones containing kinase-negative mutant EGFR. After an extended period of differentiation, the cell types present in mutant and control cultures differed. Mutant clones produced frequent cardiac and skeletal muscle as the predominant differentiated cell types in vitro; other cells types were sparse or absent. Teratocarcinomas formed by EGFR-deltakinase-expressing ES cells contained frequent skeletal and cardiac muscle as well as apoptotic nuclei, while normal ES cells produced no detectable muscle and less apoptoses. Since mutant differentiated cultures had slower growth rates and increased levels of cell death, we concluded that: (1) inactive EGFR does not allow some cell types to survive and/or proliferate; (2) tissues that do not require EGFR for their survival, development or function predominate in long-term mutant cultures; (3) EGFR activity is not necessary for cardiac and skeletal muscle or endoderm formation and (4) Impaired survival of EGF-dependent lineages leads to preferential selection of muscle in differentiating ES cells.
J X Wu; E D Adamson
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  122     ISSN:  0950-1991     ISO Abbreviation:  Development     Publication Date:  1996 Oct 
Date Detail:
Created Date:  1996-12-10     Completed Date:  1996-12-10     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  3331-42     Citation Subset:  IM    
The Burnham Institute, La Jolla Cancer Research Center, CA 92037, USA.
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MeSH Terms
Cell Death
Cell Differentiation / physiology*
Cell Line, Transformed
DNA-Binding Proteins / genetics,  metabolism
Fetal Proteins / genetics,  metabolism
Gene Expression
Keratins / genetics,  metabolism
Myosins / genetics,  metabolism
Plasminogen Activators / genetics,  metabolism
Receptor, Epidermal Growth Factor / metabolism*
T-Box Domain Proteins*
alpha-Fetoproteins / genetics,  metabolism
Grant Support
Reg. No./Substance:
0/Brachyury protein; 0/DNA-Binding Proteins; 0/Fetal Proteins; 0/T-Box Domain Proteins; 0/alpha-Fetoproteins; 68238-35-7/Keratins; EC 2.7.-/Phosphotransferases; EC, Epidermal Growth Factor; EC 3.4.21.-/Plasminogen Activators; EC

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