Introduction of an Activated N-ras Oncogene Alters the Growth Characteristics of the Interleukin 6-dependent Myeloma Cell Line ANBL6

Daniel Billadeau, Diane F. Jelinek, Nisha Shah, Tucker W. LeBien, Brian Van Ness

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

multiple myeloma (MM) is a late-stage B-cell cancer with an unknown etiology. Activating mutations of the N-ras and K-ras oncogenes occur with a high frequency in myeloma and, therefore, may play a role in the pathogenesis of the disease. To study the role of N-ras-activating mutations in the regulation of myeloma tumor growth, we introduced a con-stitutively active N-ras cDNA containing a glutamine to arginine (CAA-CGA) amino acid substitution at codon 61 into the interleukin 6 (IL-6)-dependent myeloma cell line ANBL6. Expression of the mutant N-ras cDNA resulted in significant IL-6-independent growth, as well as augmentation of growth at suboptimal concentrations of IL.-6. The IL-6-independ-ent growth pattern was not the result of activation of autocrine IL-6 production in the mutant N-ras-expressing population because neutralizing antibodies to the IL-6 receptor and to IL-6 had no effect on the rate of DNA synthesis in the absence of IL-6. Furthermore, mutant N-ras expression decreased the percentage of cells undergoing apoptosis in the absence of IL-6. These data suggest that activating mutations of the ras oncogenes may result in growth factor independence accompanied by a suppression of apoptosis in MM. Therefore, the use of therapies designed to block IL-6 action in MM may have less of an impact on tumors bearing activated ras mutations.

Original languageEnglish (US)
Pages (from-to)3640-3646
Number of pages7
JournalCancer research
Volume55
Issue number16
StatePublished - Aug 15 1995

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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