Insulin-like growth factor I is a dual effector of multiple myeloma cell growth.

摘要: Multiple myeloma (MM) is an invariably fatal disease that accounts for approximately 1% to 2% of all human cancers. Surprisingly little known about the cellular pathways contributing growth these tumors. Although cytokine interleukin-6 has been suggested be major stimulus cell growth, role a second potential factor, insulin-like factor I (IGF-I), less clearly defined. The IGF-I signaling cascade in 8 MM lines was examined. In 7 these, receptor (IGF-IR) expressed and autophosphorylated response ligand. Downstream IGF-IR, insulin substrate 1 phosphorylated, leading activation phosphatidylinositol-3′-kinase (PI-3K). PI-3K, turn, regulated 2 distinct pathways. first included Akt Bad, inhibition apoptosis; mitogen-activated protein kinase (MAPK), resulting proliferation. Biologic relevance this pathway demonstrated because vitro induced both antiapoptotic proliferative effect. Importantly, vivo administration SCID mice inoculated with OPM-2 line led twice rate tumor cells as controls. These results suggest activates at least effecting contributes significantly expansion vivo.