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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

Oncogene volume 19, pages 2704–2713 (2000)Cite this article

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.

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Acknowledgements

The authors thank Dr Mien-Chie Hung for cosmid clone cNeu-104, and pCMVHER2WT; Dr Hsin-Fang Yang-Yen for pZIP-v-H-ras; Dr Ruey-Hwa Chen for pKR5 v-src; Dr Bert Vogelstein for pWWP-Luc; and Dr Yu-Chong Lin for the critical review of the manuscript. This work was supported by Grants NSC85-2331-B002-054, NSC86-2314-B002-144 and NSC87-2314-B002-186 from National Science Council, Taipei, Taiwan, Republic of China.

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  1. Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China

    You-Chin Lin, Jei-Ming Peng & Won-Bo Wang

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Lin, YC., Peng, JM. & Wang, WB. 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. Oncogene 19, 2704–2713 (2000). https://doi.org/10.1038/sj.onc.1203582

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