ONCOGENIC CAPACITY OF THE E2F1 GENE

Previous experiments have identified the E2F transcription factor as a potential downstream target for the action of cellular regulatory act ivities, such as the Rb tumor suppressor protein, that control cell gr owth and that, when altered, contribute to the development of human tu mors. In light of these findings, we have assayed the ability of the E 2F1 and DP1 genes, which encode heterodimeric partners that together c reate E2F activity, to act in an oncogenic fashion. We find that E2F1, particularly in combination with the DP1 product, cooperates with an activated ras oncogene to induce the formation of morphologically tran sformed foci in primary rat embryo fibro blast cultures. In addition, an E2F1 chimeric protein, in which sequences involved in Rb binding ha ve been replaced with the herpesvirus VP16 activation domain, exhibits increased transformation activity. Cells transfected with E2F1 and DP 1 or the E2F1-VP16 chimera form colonies in soft agar and induce tumor formation in nude mice. We conclude that deregulated E2F1 expression and function can have oncogenic consequences.