Regulation of Bcl-2-family proteins in myeloma cells by three myeloma survival factors: interleukin-6, interferon-alpha and insulin-like growth factor 1

As survival regulation is a key process in multiple myeloma biology, we hav e studied the Bcl-2 family proteins that can be regulated by three myeloma cell survival factors: interleukin-6 (IL-6), interferon-alpha (IFN-alpha) a nd insulin-like growth factor (IGF-1). Eleven myeloma cell lines, whose sur vival and proliferation are dependent on addition of IL-6, variably express ed 10 anti-apoptotic or pro-apoptotic proteins of the Bcl-2-family. When my eloma cells from four cell lines were IL-6 starved and activated with IL-6 or IFN-alpha, we observed that only Mcl-1 expression was up-regulated with myeloma cell survival induction. Nor was obvious regulation of these 10 pro -apoptotic or anti-apoptotic proteins found with IGF-1, another potent myel oma cell survival factor. Our results indicate that the myeloma cell surviv al activity of IL-6 linked to Bcl-xL regulation cannot be generalized and e mphasize that Mcl-1 is the main target of IL-6 and IFN-alpha stimulation. H owever, other changes in the activity of the Bcl-2 protein family or other apoptosis regulators must be identified to elucidate the IGF-1 action mecha nism.