Maintenance of growth factor signaling through Ras in human colon carcinoma cells containing K-ras mutations

Annie Buard, Patricia A. Zipfel, Randall S. Frey, Kathleen M. Mulder

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Fifty percent of human colon carcinomas contain activating mutations in the K-ras gene. However, whether these alterations in K-ras affect the function of Ras proteins in growth factor (GF) signal transduction is not known. Here we have characterized a previously defined human colon carcinoma cell model system for K-ras gene mutations and for altered levels of Ras protein expression and have examined whether these alterations affect Ras function in GF signal transduction. Sequence analysis of PCR-amplified K-ras gene fragments indicated that among the more aggressive cell lines, four had a normal K-ras sequence, whereas 3 others (isolated from the same human tumor) contained a mutation at codon 13. In contrast, all 7 of the less aggressive cell lines contained a mutation at either codon 12 or 13. In addition to the presence of a K-ras mutation, one cell line expressed higher levels of the K-Ras protein and displayed elevated Ras-GTP loading (in the absence of GF addition) compared with the other cell lines examined. Despite these alterations, the mitogenic GF combination epidermal growth factor + insulin + transferrin resulted in an activation of Ras and extracellular signal-regulated kinase 2. Collectively, our results indicate that the malignant phenotype of the cell lines was not correlated with the presence of K-ras mutations or with higher levels of Ras protein expression. Furthermore, K-ras mutations, high levels of K-Ras protein expression, and elevated Ras- GTP loading, as they occur naturally in human colon carcinomas, do not abolish the function of Ras in GF signaling.

Original languageEnglish (US)
Pages (from-to)539-546
Number of pages8
JournalInternational Journal of Cancer
Volume67
Issue number4
DOIs
StatePublished - 1996

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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