Activation of N-ras and K-ras induced by interleukin-6 in a myeloma cell line: Implications for disease progression and therapeutic response

Matt Rowley, Brian Van Ness

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Ras is a major signaling molecule activated by interleukin-6. There have been no published reports, however, that specifically examine the kinetics and percentage of Ras activation in response to IL-6. Model cell lines were used to study activation of N- and K-ras induced by IL-6. All of the myeloma cell lines we tested express both N-ras and K-ras, but not H-ras. GTP-bound Ras was measured and the percentage of the total Ras pool that was activated in response to IL-6 was calculated. IL-6 is able to transiently activate both N- and K-ras in the ANBL6 cell line. In addition, increasing concentrations of IL-6 are able to activate increasing levels of both N- and K-ras. One ng/ml of IL-6 is able to activate approximately 10% of the N-ras pool and 18% of the K-ras pool. The amount of Ras-GTP in the cells correlates with the level of proliferation at low levels, but proliferation plateaus when higher levels of Ras-GTP are present. Protection from dexamethasone-induced apoptosis correlates with IL-6 concentration and Ras activation. However, IL-6 enhances apoptosis induced by doxorubicin. Interestingly, the ANBL6 cell line transfected with an N-ras12 or a K-ras12 gene is protected from doxorubicin-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)8769-8775
Number of pages7
JournalOncogene
Volume21
Issue number57
DOIs
StatePublished - Dec 12 2002

Bibliographical note

Funding Information:
We wish to thank Richard Roof and the Daniel Mueller lab for reagents and technical support for the activated Ras interaction assay. This work was supported by the National Institutes of Health grant P01CA62242.

Keywords

  • Myeloma
  • Ras
  • Therapeutic response

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