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PMID: 8189528 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Adenovirus type 9 E4 open reading frame 1 encodes a transforming protein required for the production of mammary tumors in rats.

Journal of virology ·Vol. 68 ·No. 6 ·1994-06-00 ·Pages 3917-24

Javier RT

Abstract

The E4 region of human adenovirus type 9 (Ad9) transforms established rat embryo fibroblasts and encodes an essential determinant for the production of estrogen-dependent mammary tumors in rats. Testing of the seven Ad9 E4 open reading frames (ORFs) individually for transformation of the established rat embryo fibroblast cell line CREF indicated that only Ad9 E4 ORF1 possessed a significant ability to generate transformed foci on these cells. In contrast, the E4 ORF1 sequences from human Ad5 and Ad12 lacked the transforming potential exhibited by Ad9 E4 ORF1. Cell lines derived from Ad9 E4 ORF1-transformed foci expressed the 14-kDa Ad9 E4 ORF1 protein and formed colonies in soft agar. In addition, the Ad9 E4 ORF1 protein was required for initiation of mammary oncogenesis in vivo, as E4 ORF1 mutant viruses failed while E4 ORF2 and ORF3 mutant viruses succeeded in eliciting mammary tumors in animals. A role for Ad9 E4 ORF1 in tumor maintenance was suggested by the fact that 100% of virus-induced mammary tumors expressed the E4 ORF1 protein. Taken together, the facts that the Ad9 E4 ORF1 protein exhibits transforming potential in culture and is required by Ad9 to produce mammary tumors in animals suggest that Ad9 E4 ORF1 is a new viral oncoprotein.

MeSH Terms
Adenovirus E4 Proteins/genetics,physiology Adenoviruses, Human/genetics,pathogenicity,physiology Amino Acid Sequence Animals Base Sequence Cell Line Cell Transformation, Neoplastic/genetics DNA, Viral/genetics Female Genes, Viral Humans Mammary Neoplasms, Experimental/etiology Molecular Sequence Data Mutagenesis Neoplasms, Hormone-Dependent/etiology Open Reading Frames Rats Sequence Homology, Amino Acid
Chemicals
Adenovirus E4 Proteins DNA, Viral
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Javier R T
Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030.
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.68.6.3917-3924.1994
Published
1994-06-00
Pages
3917-24
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC236897
Subset
IM
Grants
NCI NIH HHS · R01 CA058541 · United States
NCI NIH HHS · CA 58541-02 · United States
External Links
PubMed source DOI: 10.1128/JVI.68.6.3917-3924.1994 PMC Full Text View journal details
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