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Nucleic Acids Research, 1988, Vol. 16, No. 23 10973-10984
© 1988


MOLECULAR BIOLOGY

Similar effects of adenovirus E1A and glucocorticoid hormones on the expression of the metalloprotease stromelysin

R. Offringa, A.M.M. Smits, A. Houweling, J.L. Bos and A.J. van der Eb

Laboratory for Molecular Carcinogenesis, Sylvius Laboratories P0 Box 9503, 2300 RA Leiden, The Netherlands

Received September 29, 1988. Accepted November 4, 1988.

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 mechanist by which AdE1A represses cellular gene activity.


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