Use of antisense oligomers to study the role of c-jun in G1 progression.

In actively proliferating Swiss 3T3 fibroblasts, expression of the protooncogene c-jun is maximally induced early in G1, immediately after completion of mitosis. Within 2 hours, c-jun mRNA levels drop to a basal amount that is approximately 30% of the maximum. This is maintained throughout the remainder of G1. To access the functional implications of this pattern of c-jun expression, antisense oligomers specific to c-jun were added to either actively proliferating or synchronized Swiss 3T3 cells, and their ability to inhibit DNA synthesis and division was determined. Our results show that if Swiss 3T3 cells are treated with anti-c-jun while actively growing or at any time during G1 after completion of mitosis, they exhibit a reduced ability to enter S-phase and subsequently divide. These results demonstrate that the regulation of G1 progression following mitosis depends on the expression and function of the protooncogene c-jun.