Similar effects of adenovirus E1A and glucocorticoid hormones on the expression of the metalloprotease stromelysin.
The stromelysin (sml) gene encodes a secreted protease which degrades components of the extracellular matrix. Transformation of NRK49F cells by the E1A region of adenovirus (Ad) type 5 or 12 reduces sml RNA levels, whereas various growth factors or EJras-mediated transformation stimulate sml gene expression in these cells. Nuclear run-on experiments show that AdE1A, growth factors and EJras act on sml gene expression at the level of transcription. Although the sml gene is strongly suppressed in AdE1A-transformed cells, treatment with growth factors or transfection of EJras still causes a raise in sml mRNA levels, indicating that E1A does not block the induction mechanism itself. The effect of glucocorticoid hormones on sml gene expression is very similar to that of AdE1A, in that mRNA levels are lowered without affecting the induction phenomenon. This similarity may provide a clue to the mechanism by which AdE1A represses cellular gene activity.
Offringa
R
R
Laboratory for Molecular Carcinogenesis, Sylvius Laboratories, Leiden, The Netherlands.
Smits
A M
AM
Houweling
A
A
Bos
J L
JL
van der Eb
A J
AJ
D000260:Adenoviruses, Human / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D002472:Cell Transformation, Viral; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000302:isolation & purification; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects; D015291:Transforming Growth Factors / Q000494:pharmacology
D012333:RNA, Messenger; D015291:Transforming Growth Factors; D003907:Dexamethasone; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3