E1A 12S IN THE ABSENCE OF E1B OR OTHER COOPERATING ONCOGENES ENABLES CELLS TO OVERCOME APOPTOSIS

Neonatal rat kidneys are still undergoing growth and differentiation. Within 24 h after placing these cells in culture, programmed cell death has been activated. This is evidence by intranucleosomal DNA digestion. Cellular DNA synthesis and proliferation cease between 48 and 72 h after plating and the epithelial cells begin to die. The adenovirus E1A 12S gene, in the presence or absence of the E1B gene products, restarts the proliferation program of these cells, retaining their differentiated states. 12S can accomplish this in the presence and absence of serum. Expression of the E1A 13S gene results in cellular DNA degradation due to necrosis, but not apoptosis, brought on by the expression of the 13S-dependent viral genes. Those cells that retain the 12S sequences escape apoptosis and proceed to become immortal. In addition, 12S enables Madin Darby canine kidney (MDCK) epithelial cells to overcome TGF-beta 1 induced inhibition of proliferation and apoptosis. Thus, E1A 12S may be an anti-apoptotic gene.