Document Detail

Reduced expression of EphrinA1 (EFNA1) inhibits three-dimensional growth of HT29 colon carcinoma cells.
MedLine Citation:
PMID:  11741747     Owner:  NLM     Status:  MEDLINE    
Ephrin A1 (EFNA1) is a GPI-anchored ligand that preferentially binds to the receptor tyrosine kinase, EphA2. EphA2 is over-expressed in malignant melanocytes and in prostate carcinoma cells. Whether activation of EphA2 by EFNA1 is involved in aberrant growth or differentiation of cancer cells is currently not known. We studied the effect of reducing EFNA1 on the growth of a colon carcinoma cell line (HT29). HT29 cells were transfected with EFNA1 antisense yielding clones that expressed less than 25% of EFNA1 found in vector controls. EFNA1-antisense transfectants grew slower than controls when cultured as three-dimensional spheroids. When grown as monolayers, the transfectants had a similar doubling time of the vector controls. These results indicated that autocrine stimulation of EphA2 by EFNA1 could trigger an indirect growth signal by overcoming 'contact inhibition'. Following addition of EFNA1-Fc to HT29 cells, tyrosine hyperphosphorylation of EphA2, E-cadherin, and beta-catenin were observed. Because the function of E-cadherin is associated with contact inhibition of HT29 cells, phosphorylation of E-cadherin and beta-catenin by activation of EphA1 is one possible mechanism by which HT29 cells alleviate contact inhibition.
Lyka Potla; Erwin R Boghaert; Douglas Armellino; Philip Frost; Nitin K Damle
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cancer letters     Volume:  175     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2002 Jan 
Date Detail:
Created Date:  2001-12-19     Completed Date:  2002-02-01     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  187-95     Citation Subset:  IM    
Oncology/Immunology Division, Wyeth-Ayerst Research, 200/4604, 401 North Middletown Road, Pearl River, NY 10965-1299, USA.
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MeSH Terms
Base Sequence
Cell Division / drug effects,  physiology*
Cytoskeletal Proteins / metabolism
DNA Primers
Glycosylphosphatidylinositols / metabolism
HT29 Cells
Molecular Sequence Data
Oligodeoxyribonucleotides, Antisense / pharmacology
Phosphotyrosine / metabolism
Polymerase Chain Reaction
Proteins / genetics*
Time Factors
Transcription Factors / metabolism
beta Catenin
Reg. No./Substance:
0/CTNNB1 protein, human; 0/Cytoskeletal Proteins; 0/DNA Primers; 0/Ephrin-A1; 0/Ephrin-A2; 0/Glycosylphosphatidylinositols; 0/Oligodeoxyribonucleotides, Antisense; 0/Proteins; 0/Trans-Activators; 0/Transcription Factors; 0/beta Catenin; 21820-51-9/Phosphotyrosine

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