猴病毒四十型T/t-common基因用於治療HER-2/neu大量表現的癌症的評估
Date Issued
2003
Date
2003
Author(s)
王萬波
DOI
913112B002014
Abstract
We showed previously that simian virus 40 (SV40) T/t-common polypeptide,
which contains the N-terminal common domain of SV40 large T and small t antigens,
can repress HER-2/neu expression in HER-2/neu-overexpressing ovarian carcinoma
SK-OV-3 cells and consequently suppressed the tumorigenic potential of these cells
(Oncogene 19:2704-2713, 2000). To further investigate the tumor-suppressing activity
of T/t-common, we asked whether T/t-common could induce apoptosis of tumor cells.
When the T/t-common-encoding plasmid was cotransfected with a plasmid encoding
the neomycin resistance gene into HER-2/neu-overexpressing cancer cells, the
number of G418-resistant colonies obtained was much lower than that obtained with
vector cotransfection. This data suggests that T/t-common may induce cell death in
these HER-2/neu-overexpressing cancer cells. Similar experiment was also performed
with cancer cells that do not overexpress HER-2/neu and non-transformed cells. The
killing effect of T/t-common was not observed, suggesting that T/t-common may
specifically induce cell death in HER-2/neu-overexpressing cancer cells.
To further investigate the death-inducing activity of T/t-common, we asked
whether T/t-common could induce apoptosis in HER-2/neu-overexpressing cancer
cells. We first tested whether T/t-common-expressing SK-OV-3 cells underwent
apoptosis under low-serum condition. Both TUNEL and FACS analyses indicate that
this is indeed the case. We then used T/t-common-carrying adenovirus or vector
adenovirus to infect HER-2/neu-overexpressing cancer cells, low
HER-2/neu-expressing cancer cells, and non-transformed cells. Both TUNEL and
FACS analyses showed that T/t-common adenovirus infection could induce apoptosis
in HER-2-overexpressing cancer cells but not in low HER-2/neu-expressing cancer
cells and non-transformed cells. We next tested whether T/t-common induced
apoptosis through repressing HER-2/neu expression. We found that this is indeed the
case, because re-expression of a large amount of HER-2/neu in the
T/t-common-expressing cells blocked apoptosis induced by T/t-common. Taken
together, these data suggest that T/t-common could specifically induce apoptosis in
HER-2-overexpressing cancer cells and this ability of T/t-common may contribute to
its tumor-suppressing activity.
Subjects
HER-2/neu
SV40
T/t-common
Apoptosis
SDGs
Publisher
臺北市：國立臺灣大學醫學院免疫學研究所
Type
journal article
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