Putting the Oncogenic and Tumor Suppressive Activities of E2F into Context.
Deregulation of E2F transcriptional activity as a result of alterations in the p16(INK4a)-cyclin D1-Rb pathway is a hallmark of human cancer. E2F is a family of related factors that controls the expression of genes important for cell cycle progression as well as other processes such as apoptosis, DNA repair, and differentiation. Some E2F family members are associated with the activation of transcription and the promotion of proliferation while others are implicated in repressing transcription and inhibiting cell growth. It is now becoming clear however, that this view of the E2F family is overly simplistic and that the role of a given E2F in regulating transcription and cell growth is highly dependent on context. This complexity is also evident when analyzing how perturbations in E2F modulate tumor development. As expected, some E2F family members are found to be critical for mediating the oncogenic effects of Rb loss. On the other hand, several E2Fs have tumor suppressive properties in mouse models and this appears to be reflected in some human cancers with decreased E2F expression. Surprisingly, tumor suppressive activity is not associated with the repressor E2Fs but instead is associated with the same E2Fs shown to have oncogenic activities. For example, deregulated E2F1 expression can either promote or inhibit tumorigenesis depending on the nature of the other oncogenic mutations that are present. Thus, the ability of some E2F family members to behave as both oncogene and tumor suppressor gene can be reconciled by putting E2F into context.
Johnson
David G
DG
Department of Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park Research Division, Smithville, TX 78957, USA. djohnson@sprd1.mdacc.tmc.edu.
Degregori
James
J
D000818:Animals; D002471:Cell Transformation, Neoplastic; D050684:E2F Transcription Factors / Q000502:physiology*; D006801:Humans; D025521:Tumor Suppressor Proteins
D050684:E2F Transcription Factors; D025521:Tumor Suppressor Proteins