The role of Bcl-2 protein and autocrine growth factors in a human follicular lymphoma-derived B cell line.
We have shown that the ability of the human follicular lymphoma-derived cell line SU-DHL-6 to proliferate and survive in vitro depends on both Bcl-2 expression and multiple autocrine growth factors. Treatment with Bcl-2 antisense (AS Bcl-2) decreased Bcl-2 protein levels. However, a cytotoxic effect was seen only at very restricted cell densities. Below such densities cells underwent spontaneous death without any treatment, while above these cell densities no cytotoxic effect of AS Bcl-2 could be seen. The conditioned medium of SU-DHL cells supported the survival and growth of these cells cultivated at low cell densities and partially reversed the cytotoxicity associated with Bcl-2 depletion. RT/PCR analysis revealed autocrine expression of IL-1 beta, IL-2, IL-5 and TNF-beta in SU-DHL cells. Neutralizing antibodies against these cytokines inhibited SU-DHL proliferation. Thus, development of autocrine GF secretion may be the second step in the pathogenesis of follicular lymphomas.
Blagosklonny
M V
MV
Clinical Pharmacology Branch, National Cancer Institute, National Institute of Health, Bethesda, MD 20892, USA.
Neckers
L M
LM
D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D006133:Growth Substances / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D016207:Cytokines; D006133:Growth Substances; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2