title: Alternative effects of RAS and RAF oncogenes on the proliferation and apoptosis of factor-dependent FDC-P1 cells.
abstract: Despite the fact that RAF-1 lies immediately downstream of p21RAS in the MAP kinase-signalling cascade, recent evidence in non-haematopoietic environments suggest that RAS and RAF can transduce signals through alternative pathways specific to a particular cell type. Since mutational activation of RAS occurs at high frequency in human leukaemia, we have investigated the contribution of signalling from mutant RAF in mediating the transforming effects of the N-RAS oncogene in the growth factor-dependent cell line, FDC-P1. Independent activation of N-RAS extended the period of exponential growth leading to an increased saturating density under optimal growth conditions. Under conditions of growth factor withdrawal, cells expressing mutant RAS, but not control cells, demonstrated protection against apoptotic death. Although RAF promoted cell proliferation in a similar manner to that observed in FDCP-RAS cells, expression of mutant RAF was not as effective at protecting these cells against apoptotic death following growth factor withdrawal. The results suggest that RAS utilises RAF-dependent signals in promoting the proliferation of FDC-P1 cells but the anti-apoptotic effects of this oncogene are mediated through a RAF- and BCL-2-independent pathway.
authors.affiliation: LRF Differentiation Unit, University of Wales College of Medicine, Heath Park, Cardiff, UK.
authors.forename: A P
authors.initials: AP
authors.lastname: McGlynn
authors.forename: R A
authors.initials: RA
authors.lastname: Padua
authors.forename: A K
authors.initials: AK
authors.lastname: Burnett
authors.forename: R L
authors.initials: RL
authors.lastname: Darley
mesh_terms: D000782:Aneuploidy; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002455:Cell Division; D018920:Coculture Techniques; D019926:Cyclin B / Q000096:biosynthesis / Q000235:genetics; D056744:Cyclin B1; D015973:Gene Expression Regulation, Leukemic; D011905:Genes, ras; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000235:genetics / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D009857:Oncogenes; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics* / Q000502:physiology; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: C534699:CCNB1 protein, human; C534700:Ccnb1 protein, mouse; D019926:Cyclin B; D056744:Cyclin B1; D007377:Interleukin-3; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019908:Proto-Oncogene Proteins c-raf; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)