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

Overexpression of HER-2/neu (also known as c-erbB-2) proto-oncogene frequen tly occurs in many different types of human cancers, including ovarian carc inoma, and is known to enhance tumor metastasis and chemoresistance. Previo us 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 suppressi on of tumorigenicity of HER-2/neu-overexpressing cancer cells. Here we repo rt 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 transfecte d 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 it-common. Accordingly the tumorigenic potential of these T/t-common-expres sing clones, including the ability to grow anchorage-independently and the ability to induce tumor in nu/nu mice, was also drastically suppressed. Fur thermore, when T/t-common was transiently cotransfected with the activated genomic neu into NIH3T3 cells, the transforming activity of the latter was suppressed by Tit-common in soft-agarose microcolony formation assays. Take n together, these data suggest that Tit-common may act as a transformation suppressor of the HER-2/neu oncogene.