Offringa R, Smits A M, Houweling A, Bos J L, van der Eb A J
Laboratory for Molecular Carcinogenesis, Sylvius Laboratories, Leiden, The Netherlands.
Nucleic Acids Res. 1988 Dec 9;16(23):10973-84. doi: 10.1093/nar/16.23.10973.
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.
基质溶解素（sml）基因编码一种分泌型蛋白酶，该蛋白酶可降解细胞外基质的成分。5型或12型腺病毒（Ad）的E1A区域转化NRK49F细胞会降低sml RNA水平，而各种生长因子或EJras介导的转化则会刺激这些细胞中sml基因的表达。核转录实验表明，AdE1A、生长因子和EJras在转录水平上作用于sml基因表达。尽管在AdE1A转化的细胞中sml基因受到强烈抑制，但用生长因子处理或转染EJras仍会导致sml mRNA水平升高，这表明E1A本身并未阻断诱导机制。糖皮质激素对sml基因表达的影响与AdE1A非常相似，即mRNA水平降低而不影响诱导现象。这种相似性可能为AdE1A抑制细胞基因活性的机制提供线索。
