Adenovirus E1A down-regulates the EGF receptor via repression of its promoter.
The epidermal growth factor receptor (EGF-R), after activation by its ligands, stimulates a cascade of intracellular events leading to cellular proliferation. Its expression is increased in various forms of cancer as a consequence of altered regulation. Our objective was to study potential negative regulators of EGF-R expression; we investigated the effect of adenovirus E1A proteins. E1A proteins can exert both positive and negative effects on cell growth, depending on the cell type and cellular context, and have anti-tumorigenic features on human cancer cells. We show that human cell lines stably transformed with the adenovirus E1 region show significantly reduced expression of EGF-R protein and mRNA compared to their control, non-E1A-expressing counterparts. Furthermore, the promoter activity of EGF-R can be specifically repressed by E1A in transient co-transfection analysis in multiple cell types. Transfections with deleted promoter fragments and constructs containing short fragments of the putative E1A-responsive region fused to a heterologous promoter indicate that E1A-responsive elements are contained in a promoter region (from -150 to -76). Analysis of E1A mutants showed that both E1A gene products, 12S and 13S, repress EGF-R promoter activity and that full repression requires the presence of an intact CR1 domain.
Prudenziati
M
M
Laboratory of Molecular Genetics, G. Gaslini Institute, Genoa, Italy.
Sirito
M
M
van Dam
H
H
Ravazzolo
R
R
D017500:Adenovirus E1A Proteins / Q000502:physiology*; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002461:Cell Line, Transformed; D015536:Down-Regulation; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051381:Rats; D014158:Transcription, Genetic; D014162:Transfection
D017500:Adenovirus E1A Proteins; D066246:ErbB Receptors