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/neuoverexpressing
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.
