SV40 T/t-common polypeptide specifically induces apoptosis in human cancer cells that overexpress HER2/neu
Journal
Cancer Research
Journal Volume
66
Journal Issue
11
Pages
5847-5857
Date Issued
2006
Author(s)
Wen C.-C.
Cheng S.-A.
Hsuen S.-P.
Huang Y.-L.
Kuo Z.-K.
Lee H.-F.
Kuo C.-H.
Du J.-L.
WON-BO WANG
Abstract
Previously, we reported that SV40 T/t-common polypeptide, which contains the NH2-terminal common domain of SV40 large T and small t antigens, can repress HER2/neu (also known as erbB-2) expression and consequently suppress the tumorigenic potential of the HER2/neu-overexpressing ovarian carcinoma cells. Here we report that T/t-common could specifically induce apoptosis in HER2/neu-overexpressing human cancer cell lines but not in nontransformed cell lines and HER2/neu low-expressing human cancer cell lines. The ability of T/t-common to induce apoptosis in HER2/neu-overexpressing cancer cells was derived from its ability to inhibit HER2/neu because reexpression of a large amount of HER2/neu could block apoptosis induced by T/t-common. T/t-common expression in HER2/neu-overexpressing SK-OV-3 cancer cells led to down-regulation of Bcl-2 and Bcl-XL, and overexpression of Bcl-2 could inhibit the ability of T/t-common to induce apoptosis in these cells. Therefore, the apoptosis-inducing activity of T/t-common is related to its ability to inhibit Bcl-2 expression in HER2/neu-overexpressing cancer cells. Consistent with the apoptosis-inducing activity of T/t-common, we found that T/t-common could specifically inhibit the soft-agarose colony-forming ability of the HER2/neu-overexpressing human cancer cell lines but not that of the HER2/neu low-expressing human cancer cell lines. Finally, we showed that T/t-common could specifically sensitize HER2/neu-overexpressing human cancer cell lines, but not HER2/neu low-expressing human cancer cell lines, to chemotherapeutic agent etoposide. Together, these data suggest that T/t-common alone or in combination with chemotherapy may provide a new approach for treatment of cancers that overexpress HER2/neu. ?2006 American Association for Cancer Research.
SDGs
Other Subjects
agarose; antineoplastic agent; epidermal growth factor receptor 2; etoposide; polypeptide; protein bcl 2; protein bcl xl; virus large T antigen; virus small T antigen; animal cell; apoptosis; article; cancer cell; cancer cell culture; cancer inhibition; carcinogenic activity; carcinogenicity; colony formation; controlled study; cytotoxicity; down regulation; drug activity; drug potentiation; drug sensitization; gene expression; gene overexpression; gene repression; human; human cell; nonhuman; oncogene neu; priority journal; Simian virus 40; Antigens, Polyomavirus Transforming; Apoptosis; Apoptosis Regulatory Proteins; Cell Line, Tumor; Cell Transformation, Neoplastic; Gene Therapy; Hela Cells; Humans; Neoplasms; Protein Structure, Tertiary; Receptor, erbB-2; Transfection
Type
journal article