c-jun cooperates with SV40 T-antigen to sustain MMP-2 expression in immortalized cells

The c-jun gene is a major regulator of proliferative and stress responses o f both normal and transformed cells, In general, during immortalization/tra nsformation c-jun cooperates with oncogenic signals rather than acting as a n oncogene itself. Here we report a novel example of this cooperation, the requirement for c-jun to sustain expression of the matrix metalloproteinase -a (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 t umor microenvironments. We used wild-type and c-jun null primary and TAg-im mortalized mouse embryonic fibroblasts (mEFs) to investigate the importance of c-jun for the regulation of this activity, and observed that c-jun is e ssential for MMP-2 expression in immortalized but not primary mEFs. This fi nding directly demonstrates a cooperative interaction of c-jun with an onco gene, and suggests that TAg dependent immortalization/transformation may re quire other c-Jun/AP-1-dependent genes. (C) 2001 Academic Press.