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 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.
Laderoute
K R
KR
SRI International, 333 Ravenswood Avenue, Menlo Park, California 94025, USA. keith.laderoute@sri.com
Calaoagan
J M
JM
Knapp
A M
AM
Mendonca
H L
HL
Johnson
R S
RS
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000494:pharmacology*; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D017364:Collagenases / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D051379:Mice; D008970:Molecular Weight; D016755:Proto-Oncogene Proteins c-jun / Q000494:pharmacology*; D012190:Retroviridae / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
D000952:Antigens, Polyomavirus Transforming; D016755:Proto-Oncogene Proteins c-jun; D017364:Collagenases; D020778:Matrix Metalloproteinase 2