McGlynn, Angela P., Padua, Rose Ann, Burnett, Alan Kenneth and Darley, Richard Lawrence  ORCID: https://orcid.org/0000-0003-0879-0724
2000.
Alternative effects of RAS and RAF oncogenes on the proliferation and apoptosis of factor-dependent FDC-P1 cells.
Leukemia Research
24
(1)
, pp. 47-54.
10.1016/s0145-2126(99)00159-9
|
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.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Medicine |
| Subjects: | R Medicine > R Medicine (General) |
| Uncontrolled Keywords: | Aneuploidy,Animals,Apoptosis/genetics*,CellDivision,CocultureTechniques,CyclinB/biosynthesis,CyclinB/genetics,CyclinB1,GeneExpressionRegulationLeukemic*,Genesras*,GranulocyteMacrophageColonyStimulatingFactor/pharmacology,Humans,Interleukin-3/pharmacology,Leukemia Myeloid/genetics,Leukemia Myeloid/pathology*,MAP Kinase Signaling System/genetics,MAP Kinase Signaling System/physiology,Mice,Neoplasm Proteins/genetics*,Neoplasm Proteins/physiology,Oncogenes*,Proto-Oncogene Proteins c-raf/genetics*,Proto-Oncogene Proteins c-raf/physiology,Proto-Oncogene Proteins p21(ras)/physiology*,RNA Messenger/biosynthesis,RNA Messenger/genetics,Recombinant Proteins/pharmacology,Signal Transduction/genetics*,Signal Transduction/physiology,Tumor Cells Cultured/drug effects,Tumor Cells Cultured/metabolism,Tumor Cells, Cultured/pathology Substances CCNB1 protein human,Ccnb1 protein mouse,Cyclin B,Cyclin B1,Interleukin-3,Neoplasm Proteins,RNA Messenger,Recombinant Proteins,Granulocyte-Macrophage Colony-Stimulating Factor,Proto-Oncogene Proteins c-raf,HRAS protein human,Proto-Oncogene Proteins p21(ras) |
| Additional Information: | Publication Types Comparative Study Research Support, Non-U.S. Gov't Full Text Sources Elsevier Science Medical KRAS Gene - Genetics Home Reference |
| Publisher: | Elsevier |
| ISSN: | 0145-2126 |
| Related URLs: | |
| Last Modified: | 25 Oct 2022 09:25 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/58436 |
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