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 Academic Article uri icon

Overview

MeSH Major

  • Carcinoembryonic Antigen
  • Colonic Neoplasms
  • Lectins
  • ras Proteins

abstract

  • Previous studies of cell lines derived from human colon carcinoma showed that the extent of beta1-6 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 beta1-6 branching could select for cells having a lower level of K-Ras protein and Ras-activation. PHA-L binds specifically to the beta1-6 branch in N-linked carbohydrate. We utilized a K-ras mutant colon carcinoma cell line, HTB39, which had abundant beta1-6 branching and high levels of K-Ras mutant protein. Lectin resistant cell populations of HTB39 were generated and found to have less beta1-6 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 beta1-6 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 beta1-6 branching of N-linked carbohydrate and CEA production were linked to K-Ras protein synthesis and activation of the Ras-signaling pathway.

publication date

  • June 16, 1999

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1006/bbrc.1999.0819

PubMed ID

  • 10364462

Additional Document Info

start page

  • 588

end page

  • 93

volume

  • 259

number

  • 3