Transcriptional regulation of c-Jun expression during late G1/S in normal human cells is lost in human tumor cells.

Previous results from our laboratory have identified a second peak in steady state levels of c-jun mRNA (in addition to the immediate early induction) which occurs at the G1/S border in WI-38 normal human diploid fibroblasts. The present studies were undertaken in an attempt to determine (1) the molecular mechanism responsible for the expression of c-jun in late G1/S, (2) the relationship between this second peak of c-jun mRNA expression and the induction of DNA synthesis and (3) whether this cell cycle specific c-jun expression is deregulated in transformed cells. Our results show that the second peak in steady state levels of c-jun mRNA is the result of new transcription during late G1 and not altered stability of the c-jun mRNA transcribed during G1. We also show that this second peak of expression still occurs even when DNA synthesis is inhibited by either hydroxyurea or aphidicolin. Thus, the second peak precedes and is independent of DNA synthesis. Finally, we find that while two other normal human fibroblast cell lines exhibit a second peak of c-jun mRNA during late G1/S, c-jun expression is not cell cycle-regulated but rather is constitutively expressed in a number of distinct transformed cell lines. Since events occurring throughout G1 are known to regulate cell growth, our results suggest that the extent of regulation of c-jun expression during G1 may affect molecular events which ultimately lead to altered growth control as a result of cellular transformation.