E2F1 selects tumour cells for both life and death.
E2F1 is a transcription factor involved in both cell cycle progression and apoptosis. Perhaps surprisingly, these two processes are closely related, and the choice between them appears to be made on the basis of the aggregate of signals flowing into the cell at the time. This may be the means whereby normal cells tune their threshold for apoptosis with respect to the availability of external growth factors, so that cells that are supernumerary to the tissue's needs at the time can be immediately deleted. In many tumours, however, the pathways that link E2F1 activity to apoptosis have been interrupted, sometimes at multiple points. Non-small-cell lung carcinoma provides a striking example of this, with the result that expression of E2F1 in these tumours does not correlate with apoptosis but is a good surrogate marker for replicative status. This relationship does not necessarily pertain in other tumour types. Molecules such as E2F1 lie at the core of very significant cell fate decisions, but they are part of a complex matrix of interactions, all of which must be surveyed before interpretation in terms of tumour behaviour is possible. Microarray analysis may provide a way to do this. In the future, however, such interpretations, including predictions of therapeutic response, may be possible through interrogation of the status of a relatively limited number of molecules. Those that preside over critical cellular decision forks (such as the choice between proliferation or death) are good candidates for this role. E2F1 clearly qualifies as one member of this group.
Wyllie
Andrew H
AH
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
D017209:Apoptosis / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000502:physiology*; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D009363:Neoplasm Proteins; D014157:Transcription Factors