Characterization of lectin resistant cell populations derived from human colon carcinoma: Correlation of K-Ras with β1-6 branching of N-linked carbohydrate and CEA production Journal Article
| Authors: | Wojciechowicz, D. C.; Mallon, R. G.; Picon, A.; Paty, P. B. |
| Article Title: | Characterization of lectin resistant cell populations derived from human colon carcinoma: Correlation of K-Ras with β1-6 branching of N-linked carbohydrate and CEA production |
| Abstract: | Previous studies of cell lines derived from human colon carcinoma showed that the extent of β1-6 branching on N-linked carbohydrate was associated with the presence of K-ras mutation and Ras-activation. We observed that the extent of Ras-activation in these cell lines depends not only upon the presence of an activating mutation in K-ras, but also on the amount of total K-Ras protein produced. Here we examined whether negative selective pressure by PHA-L against β1-6 branching could select for cells having a lower level of K-Ras protein and Ras-activation. PHA-L binds specifically to the β1-6 branch in N-linked carbohydrate. We utilized a K-ras mutant colon carcinoma cell line, HTB39, which had abundant β1-6 branching and high levels of K-Ras mutant protein. Lectin resistant cell populations of HTB39 were generated and found to have less β1-6 branching and less K-Ras protein than their parental counterpart. The lectin resistant cell populations produced lower levels of highly glycosylated CEA which contributed to the lower level of β1-6 branching in these cells. PHA-L resistant cell populations were two-fold less sensitive than the parental line to an inhibitor of farnesyl transferase (an enzyme essential for Ras processing and function). This suggested a decrease in dependence on K-ras mediated signaling. Collectively, the data indicated that β1-6 branching of N-linked carbohydrate and CEA production were linked to K-Ras protein synthesis and activation of the Ras-signaling pathway. |
| Keywords: | signal transduction; controlled study; oncoprotein; human cell; mutant protein; carcinoembryonic antigen; protein binding; colonic neoplasms; dose-response relationship, drug; tumor cells, cultured; enzyme inhibitor; cell population; gene activation; enzyme inhibitors; ras proteins; oncogene k ras; colon carcinoma; methionine; lectin; protein glycosylation; lectins; asparagine linked oligosaccharide; precipitin tests; humans; human; priority journal; article; farnesyl trans transferase; phytohemagglutinins |
| Journal Title: | Biochemical and Biophysical Research Communications |
| Volume: | 259 |
| Issue: | 3 |
| ISSN: | 0006-291X |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 1999-06-16 |
| Start Page: | 588 |
| End Page: | 593 |
| Language: | English |
| DOI: | 10.1006/bbrc.1999.0819 |
| PUBMED: | 10364462 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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