Expression of the bcl-2 family of pro- and anti-apoptotic genes in multiple myeloma and normal plasma cells: regulation during interleukin-6(IL-6)-induced growth and survival.
Aberrant expression of genes regulating apoptosis/survival seems to be essential in the stepwise development of human multiple myeloma (MM). In this paper we have compared the expression of bcl-2 family pro- and anti-apoptotic genes in MM cell lines, primary MM cells and normal plasma cells. The Bcl-2, Mcl-1, Bcl-xL/S, Bcl-w, Bax, Bak, and Bad were shown to be expressed in both malignant and non-neoplastic, normal plasma cells. Quantitative analysis revealed that the malignant phenotype seemed to correlate with an elevated expression of Mcl-1, a decreased expression of Bax and, to a lesser extent, an increased Bcl-2/Bax expression ratio. The possible influence of interleukin-6 (IL-6) in regulating the expression of the bcl-2-related genes was also examined. Using the IL-6-dependent MM cell lines U-1958 and U-266-1970 it was clearly shown that IL-6 deprivation induced cell cycle arrest in both cell lines, whereas apoptosis was only detected in the U-1958 cells. Furthermore, the anti-apoptotic proteins Bcl-2, Mcl-1 and Bcl-xL were down-regulated, while the expression of the pro-apoptotic Bax protein was increased. To conclude, we suggest that the expression pattern of the Bcl-2 family of proteins separates the malignant phenotype of MM from normal plasma cells, and that the protecting effect of IL-6 may be conducted via an altered balance between these proteins.
D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019254:Genes, bcl-2 / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D010950:Plasma Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D014407:Tumor Cells, Cultured
D015850:Interleukin-6