Ectopic expression of eIF-4E in human colon cancer cells promotes the stimulation of adhesion molecules by transforming growth factorbeta.
Transforming growth factor beta1 (TGFbeta) inhibits cellular proliferation, promotes differentiation, and stimulates the expression and secretion of the extracellular matrix adhesion molecules fibronectin and laminin and the colon-associated intercellular adhesion molecule carcinoembryonic antigen. This is collectively called the TGFbeta-mediated adhesion response and occurs in the human colon cancer cell line Moser while the cell line KM12SM is relatively unresponsive to TGFbeta. We have previously shown that TGFbeta rapidly stimulates protein kinase C (PKC) phosphotransferase activity in the Moser cells and that the induction of the adhesion response (but not antiproliferation) by TGFbeta is dependent on PKC. Because resistance to growth factors may be due to translational suppression and the translation initiation factor eIF-4E may alleviate translational suppression, we determined the effect of eIF-4E expression on the responses of Moser and KM12SM cells to TGFbeta. Ectopic expression of eIF-4E in the TGFbeta-responsive Moser cells enhanced the activation of PKC by TGFbeta and the induction of the adhesion response, especially the secretion of adhesion molecules, but not the antiproliferative response. Ectopic expression of eIF-4E in the TGFbeta-resistant KM12SM cells increased TGFbeta stimulation of PKC and the TGFbeta-mediated adhesion response (but not antiproliferation). The secretion of adhesion molecules was significantly increased by TGFbeta. These results showed in these cells that eIF-4E promotes TGFbeta-regulated adhesion but not antiproliferation in a PKC-dependent manner.
Rajagopal
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Division of Pathology and Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Chakrabarty
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D002272:Carcinoembryonic Antigen / Q000378:metabolism; D002448:Cell Adhesion; D002455:Cell Division; D003110:Colonic Neoplasms / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D039561:Eukaryotic Initiation Factor-4E; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000096:biosynthesis*; D011485:Protein Binding; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D002272:Carcinoembryonic Antigen; D039561:Eukaryotic Initiation Factor-4E; D005353:Fibronectins; D007797:Laminin; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D011493:Protein Kinase C