Suppression of programmed death and G1 arrest in B-cell hybridomas by interleukin-6 is not accompanied by altered expression of immediate early response genes.
The murine B-cell hybridoma B9 requires interleukin-6 (IL-6) for its survival and proliferation in vitro. We show here that withdrawal of IL-6 from B9 cultures results in programmed death, concomitant with arrest of the cells in the G1 phase of the cell cycle. Unlike several other systems that undergo programmed cell death, no induction of transcripts corresponding to the testosterone-repressed message-2 or transglutaminase genes is observed during this process. Upon readdition of IL-6 to G1-arrested B9 cells, viability is maintained and entry into S phase occurs after a lag period of 10 to 12 hr. Northern blot analysis showed that the immediate-early mRNAs normally induced shortly after growth factor stimulation in quiescent fibroblasts (c-fos, c-jun, Egr-1, c-myc, JE, and KC), and other growth-related genes (2F1, c-Ha-ras, and p53), are either not induced or remain unchanged during G1 to S phase progression. A correlation was found, however, between the temporal pattern of expression of several G1/S phase genes (dihydrofolate reductase, thymidine kinase, transferrin receptor, and histone H3) and DNA synthesis. These results demonstrate that IL-6-induced viability and growth of hybridoma (and, presumably, plasmacytoma) cells is mediated via novel signal transduction pathways.
Department of Experimental Oncology, Ottawa Regional Cancer Centre, University of Ottawa, Ontario, Canada.
L A
LA
Sabourin
R G
RG
Hawley
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D003513:Cycloheximide / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D006825:Hybridomas / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D015850:Interleukin-6 / Q000494:pharmacology*; D007399:Interphase / Q000187:drug effects*; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D011519:Proto-Oncogenes; D012313:RNA / Q000096:biosynthesis; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*; D013936:Thymidine / Q000378:metabolism; D014158:Transcription, Genetic; D014404:Tubulin / Q000235:genetics; D014529:Uridine / Q000378:metabolism
D015850:Interleukin-6; D012333:RNA, Messenger; D014404:Tubulin; D012313:RNA; D003513:Cycloheximide; D013936:Thymidine; D014529:Uridine