Identification of adenovirus-type 12 gene products involved in transformation and oncogenesis

Deletion mutants of region E1 a of AD12 E1 plasmids: Effect on oncogenic transformation

“…Cells transformed by such mutant plasmids carrying deletions in the genes coding for these proteins are not tumorigenic in nude mice, which demonstrates that the Elb gene products have an important role in determining the oncogenicity of transformed cells (Jochemsen et aL, 1982;Bernards et aL, 1983). This is further confirmed by our finding that the degree of oncogenicity in nude mice of cells transformed by Ad5 or Ad12 is determined by the identity of the Elb 60-kDa protein (Bernards et al, 1983).…”

“…First, the Ela-encoded 13 S mRNA, or its translation product, is required for initi- ation of transcription of the Elb region (Bos and ten Wolde-Kraamwinkel, 1983). Since Elb expression is essential for complete transformation (Jochemsen et aL, 1982;Bernards et aL, 1983), it follows that the Ela activity which induces this expression is essential also. Several lines of evidence (Berk et aL, 1979;Jones and Shenk, 1979) indicate that expression of other early adenovirus genes is also controlled by region Ela.…”

“…Since the two genes that are specified by the Elb region (19-and 60-kDa) are also both needed for oncogenicity (Jochemsen et al, 1982;Bernards et aZ., 1983), it follows that this property requires essentially the coordinated expression of the entire El region.…”

Role of adenovirus types 5 and 12 early region 1 b tumor antigens in oncogenic transformation

“…Since cells transformed by the Ad12 Hind111 G fragment, which lack an intact 54kD Elb T-antigen, are also nononcogenic in nude mice (Jochemsen et al, 1982) we conclude that both Elb tumor antigens play an important role in oncogenesis of the transformed cell. Second, the difference in oncogenic poten-tial between Ad5-and AdlZ-transformed cells is encoded by the large (54-58kD) Elb tumor antigen.…”

“…All human adenoviruses, however, have the capacity to transform rodent cells in vitro (Flint, 1980). Rat cells transformed by oncogenic adenoviruses are tumorigenic when injected into syngeneic rats (Freeman et al, 1967;Shiroki et aL, 1977;Mak et aL, 1979;Harwood and Gallimore, 1975) and in athymic nude mice (Gallimore and Paraskeva, 1980;Bernards et al, 1982;Jochemsen et a& 1982), while cells transformed by nononcogenic adenoviruses are nononcogenie in syngeneic rats (McAllister et aL, 1969;Harwood and Gallimore, 1975) and only weakly oncogenic in nude mice (Gallimore et aL, 1977;Gallimore and Paraskeva, 1980;Bernards et uL, 1982). It is not known which gene(s) are responsible for ' To whom reprint requests should be addressed.…”