Laderoute K R, Calaoagan J M, Knapp A M, Mendonca H L, Johnson R S
SRI International, 333 Ravenswood Avenue, Menlo Park, California 94025, USA.
Biochem Biophys Res Commun. 2001 Jun 29;284(5):1134-9. doi: 10.1006/bbrc.2001.5109.
The c-jun gene is a major regulator of proliferative and stress responses of both normal and transformed cells. In general, during immortalization/transformation c-jun cooperates with oncogenic signals rather than acting as an oncogene itself. Here we report a novel example of this cooperation, the requirement for c-jun to sustain expression of the matrix metalloproteinase-2 (MMP-2) gene in cells immortalized by SV40 large T-antigen (TAg). MMP-2 encodes a type IV collagenase that is secreted by cells within normal and tumor microenvironments. We used wild-type and c-jun null primary and TAg-immortalized mouse embryonic fibroblasts (mEFs) to investigate the importance of c-jun for the regulation of this activity, and observed that c-jun is essential for MMP-2 expression in immortalized but not primary mEFs. This finding directly demonstrates a cooperative interaction of c-jun with an oncogene, and suggests that TAg dependent immortalization/transformation may require other c-Jun/AP-1-dependent genes.
