title: Enhanced ras oncogene mediated cell transformation and tumorigenesis by adenovirus 2 mutants lacking the C-terminal region of E1a protein.
abstract: Mutants of adenovirus 2 E1a defective in coding for the C-terminal 61 or 67 amino acids of a 243 amino acid (243R) protein are defective in immortalization of primary baby rat kidney (BRK) cells. However, they cooperate with T24 ras in oncogenic transformation more efficiently than wt. BRK cells transformed by the E1a C-terminal mutants and T24 ras induce rapidly growing tumors in syngeneic rats and athymic mice whereas cells transformed by the wt 243R and ras oncogene are not tumorigenic in syngeneic rats and can only induce slowly growing tumors in athymic mice. Cells transformed by the E1a mutants and ras oncogene also induce rapid metastatic tumors whereas cells transformed by the wt 243R and T24 ras can not do so. The increased tumorigenic ability exhibited by the 243R mutants does not appear to be due to differential levels of expression of p21 ras. Our results suggest that the C-terminal region of the 243R protein may have a novel function in suppression of cell transformation, tumorigenesis and tumor progression.
authors.affiliation: Institute for Molecular Virology, St. Louis University Medical Center, Missouri 63110.
authors.forename: T
authors.initials: T
authors.lastname: Subramanian
authors.forename: M
authors.initials: M
authors.lastname: La Regina
authors.forename: G
authors.initials: G
authors.lastname: Chinnadurai
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D017456:Adenovirus Early Proteins; D000818:Animals; D002471:Cell Transformation, Neoplastic; D011905:Genes, ras; D051379:Mice; D009154:Mutation; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000209:etiology*; D015689:Oncogene Protein p21(ras); D009856:Oncogene Proteins, Viral / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D017456:Adenovirus Early Proteins; D009856:Oncogene Proteins, Viral; D015689:Oncogene Protein p21(ras)