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 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. Oncogene (2000).
Lin
Y C
YC
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.
Peng
J M
JM
Wang
W B
WB
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics*; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D016147:Genes, Tumor Suppressor; D018734:Genes, erbB-2; D006801:Humans; D051379:Mice; D000090063:Proto-Oncogene Mas; D013539:Simian virus 40 / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000957:Antigens, Viral, Tumor; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas