The N-terminal common domain of simian virus 40 large T and small t antigens acts as a transformation suppressor of the HER-2/neu oncogene
Journal
Oncogene
Journal Volume
19
Journal Issue
22
Pages
2704-2713
Date Issued
2000
Author(s)
Lin Y.-C.
Peng J.-M.
WON-BO WANG
Abstract
Overexpression of HER-2/neu (also known as c-erbB-2) proto-oncogene frequently occurs in many different types of human cancers, including ovarian carcinoma, and is known to enhance tumor metastasis and chemoresistance. Previous studies showed that inhibition of HER-2/neu expression by various agents, such as adenovirus E1A and simian virus 40 large T, can lead to suppression of tumorigenicity of HER-2/neu-overexpressing cancer cells. Here we report that T/t-common, which contains the N-terminal common domain of simian virus 40 large T and small t antigens, could specifically repress the HER-2/neu promoter. When the coding sequence of T/t-common was stably transfected into the HER-2/neu-overexpressing human ovarian carcinoma SK-OV-3 cells, the expression of HER-2/neu was dramatically reduced by the expression of T/t-common. Accordingly the tumorigenic potential of these T/t-common-expressing clones, including the ability to grow anchorage-independently and the ability to induce tumor in nu/nu mice, was also drastically suppressed. Furthermore, when T/t-common was transiently cotransfected with the activated genomic neu into NIH3T3 cells, the transforming activity of the latter was suppressed by T/t-common in soft-agarose microcolony formation assays. Taken together, these data suggest that T/t-common may act as a transformation suppressor of the HER-2/neu oncogene.
Subjects
HER-2/neu; Simian virus 40 (SV40); Small t antigen; T/t-common; Tumor suppressor
SDGs
Other Subjects
virus large T antigen; virus small T antigen; Adenovirus; amino terminal sequence; animal experiment; animal model; article; carcinogenicity; colony formation; controlled study; female; fibroblast; gene expression; genetic transformation; human; human cell; metastasis; mouse; nonhuman; oncogene neu; ovary carcinoma; priority journal; promoter region; Simian virus 40; Adenoviridae; Animalia; RNA viruses; Simiae; Simian virus; Simian virus 40
Publisher
Nature Publishing Group
Type
journal article