Ras isoform abundance and signalling in human cancer cell lines.
Omerovic, J, et al.
Oncogene, 27: 2754-62 (2008)
2008
显示摘要
The ubiquitously expressed major Ras isoforms: H-, K- and N-Ras, are highly conserved, yet exhibit different biological outputs. We have compared the relative efficiencies with which epidermal or hepatocyte growth factor activates Ras isoforms and the requirement for specific isoforms in the activation of downstream pathways. We find that the relative coupling efficiencies to each Ras isoform are conserved between stimuli. Furthermore, in both cases, inhibition of receptor endocytosis led to reduced N- and H-Ras activation, but K-Ras was unaffected. Acute knockdown of each isoform with siRNA allows endogenous Ras isoform function and abundance to be probed. This revealed that there is significant variation in the contribution of individual isoforms to total Ras across a panel of cancer cell lines although typically K> or =N>H. Intriguingly, cancer cell lines where a significant fraction of endogenous Ras is oncogenically mutated showed attenuated activation of canonical Ras effector pathways. We profiled the contribution of each Ras isoform to the total Ras pool allowing interpretation of the effect of isoform-specific knockdown on signalling outcomes. In contrast to previous studies indicating preferential coupling of isoforms to Raf and PtdIns-3-kinase pathways, we find that endogenous Ras isoforms show no specific coupling to these major Ras pathways. | 17998936
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Expression profile of genes in non-small cell lung carcinomas from long-term surviving patients.
Volm, Manfred, et al.
Clin. Cancer Res., 8: 1843-8 (2002)
2002
显示摘要
Non-small cell lung cancer (NSCLC) is usually associated with a poor prognosis. Some patients survive their disease, and the underlying molecular mechanisms are still poorly understood. The purpose of this investigation was to evaluate expression profiles of proteins determining the survival of NSCLC patients for 5 years. | 12060626
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