MULTIPLE MEMBERS OF THE E2F TRANSCRIPTION FACTOR FAMILY ARE THE PRODUCTS OF ONCOGENES

The retinoblastoma gene product (pRB) is a known tumor suppressor, cap able of arresting growth in mid-to-late G(1). Part of its growth suppr ession action arises from interaction(s) with one or more members of t he E2F family of transcription factors. These proteins most likely con tribute to progression from G(0) to S phase in mammalian cells, and pR B binding most likely inhibits aspects of their suspected growth-promo ting function. Given their growth-stimulating potential, we asked whet her one or more E2F alleles can function as oncogenes. Uncloned pools of NIH 3T3 cells producing the PRE binding target E2F-1, E2F-2, or E2F -3 grew in semisolid medium. In addition, they grew to much higher sat uration density than controls. From the study of cells producing selec ted E2F-1 mutant species, it appears that E2F DNA-binding function con tributes to, and pRB/E2F binding suppresses, soft-agar growth. Thus, t hree E2F family members can act as oncogene products, suggesting that part of the normal role of pRB is to down-modulate this potential acti vity.