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Mutations in the E1a gene of type 5 adenovirus result in oncogenic transformation of fischer rat embryo cells
Author(s) -
Duigou Gregory J.,
Babiss Lee E.,
Liaw WenShing,
Zimmer Stephen G.,
Ginsberg Harold S.,
Fisher Paul B.
Publication year - 1987
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240330206
Subject(s) - mutant , biology , microbiology and biotechnology , gene , transformation (genetics) , embryo , clone (java method) , mastadenovirus , cell culture , phenotype , adenoviridae , malignant transformation , virology , genetic enhancement , cancer research , genetics
Transformation of a specific clone of Fischer rat embryo (CREF) cells with wild‐type 5 adenovirus (Ad5) or the Ela plus Elb transforming gene regions of Ad5 results in epithelioid transformants that grow efficiently in agar but that do not induce tumors when inoculated into nude mice or syngeneic Fischer rats. In contrast, CREF cells transformed by a host‐range Ad5 mutant. H5hrl, which contains a single base‐pair deletion of nucleotide 1055 in Ela resulting in a 28‐kd protein (calculated) in place of the wild‐type 51‐kd acidic protein, display a cold‐sensitive transformation phenotype and an incomplete fibroblastic morphology but surprisingly do induce tumors in nude mice and syngeneic rats. Tumors develop in both types of animals following injection of CREF cells transformed by other cold‐sensitive Ad5 Ela mutants (H5dl 101 and H5in l06), which contain alterations in their 13S mRNA and consequently truncated 289AA proteins. CREF cells transformed with only the Ela gene (0–4.5 m.u.) from H5hrl or H5dll01 also produce tumors in these animals. To directly determine the role of the 13S Ela encoded 289AA protein and the 12S Ela encoded 243AA protein in initiating an oncogenic phenotype in adenovirus‐transformed CREF cells, we generated transformed cell lines following infection with the Ad2 mutant pm975. which synthesizes the 289AA Ela protein but not the 243AA protein, and the Ad5 mutant H5dl 520 and the Ad2 mutant H2dl 1500, which do not produce the 289AA Ela protein but synthesize the normal 243AA Ela protein. All three types of mutant adenovirus‐transformed CREF cells induced tumors in nude mice and syngeneic rats. Tumor formation by these mutant adenovirus‐transformed CPEF cells was not associated with changes in the arrangement of integrated adenovirus DNA or in the expression of adenovirus early genes. These results indicate, therefore, that oncogenic transformation of CREF cells can occur in the presence of a wild‐type 13S Ela protein or a wild‐type 12S Ela protein when either protein is present alone, but does not occur when both wild‐type Ela proteins are present.