Abstract
The deregulation of the HER-2/neu protooncogene was demonstrated in a wide variety of human cancers and shown to be correlated with the progress of malignancy and metastasis in animal models. Repression of HER-2/neu overexpression suppressed the malignant phenotypes of HER-2/neu-overexpressing cancer cells. This suggested that HER-2/neu may be a good target for developing anti-cancer drugs. We found a deletion mutant of simian virus 40 (SV40) large T antigen (LT) suppresses the HER-2/neu oncogene expression at the transcriptional level. PCR clones of this mutant SV40LT, named LT425, which contains the N-terminal region of amino acid residues 1-178 of SV40LT, were subcloned and stably transfected into the HER-2/neu-overexpressing human ovarian cancer SKOV3.ip1 cells. These LT425 clones were found to be able to downregulate the endogenous production of p185HER-2/neu. In addition, the LT425-expressing stable transfectants showed reduced growth rate, low soft agarose colony forming ability, and low tumorigenic potential as compared with the parental line. These data suggested that the N-terminal 178 amino acids domain only of SV40LT may act as a transforming repressor of HER-2/neu oncogene.
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Kao, MC., Liu, GY., Chuang, TC. et al. The N-terminal 178-amino-acid domain only of the SV40 large T antigen acts as a transforming suppressor of the HER-2/neu oncogene. Oncogene 16, 547–554 (1998). https://doi.org/10.1038/sj.onc.1201513
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DOI: https://doi.org/10.1038/sj.onc.1201513
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