E1A products of adenoviruses reduce the expression of cellular proliferation-associated genes.

Products of the adenovirus (Ad) E1A region are capable of modulating the expression of a variety of genes, both of viral and cellular origin. We have investigated the expression of two proliferation-associated genes, c-myc and JE, in various adenovirus-transformed cell lines. Rodent and human cell lines, transformed as primary cultures by the E1 region of Ad5 or of Ad12, exhibit a markedly reduced expression of both genes. Ad5 E1-transformed cells show a more pronounced reduction of c-myc RNA than Ad12 E1-transformed cells. Even the very low levels of E1A products in Ad5 E1A-immortalized cells are sufficient for this reduction. Analysis of c-myc and JE expression in cell lines, transformed by other viral or cellular oncogenes, indicated that this reduction is specific for adenoviruses. These observations show that E1A does not contribute to cellular transformation by activating the proliferation-associated genes c-myc and JE, but instead suggest an alternative mechanism of E1A-mediated transformation.