SV40 T/t-common polypeptide specifically induces apoptosis in human cancer cells that overexpress HER2/neu

• Published in: Cancer research (Chicago, Ill.) Ill.), 2006-06, Vol.66 (11), p.5847-5857
• Main Authors: WEN, Chun-Chiang, CHENG, Shih-An, HSUEN, Shu-Ping, HUANG, Ya-Ling, KUO, Zong-Keng, LEE, Hsin-Fang, KUO, Chou-Hua, DU, Jia-Ling, WANG, Won-Bo
• Format: Article
• Language: English
• Subjects: Antigens, Polyomavirus Transforming - biosynthesis; Antigens, Polyomavirus Transforming - genetics; Antigens, Polyomavirus Transforming - physiology; Antineoplastic agents; Apoptosis - physiology; Apoptosis Regulatory Proteins - metabolism; Biological and medical sciences; Cell Line, Tumor; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Genetic Therapy - methods; HeLa Cells; Humans; Medical sciences; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Pharmacology. Drug treatments; Protein Structure, Tertiary; Receptor, ErbB-2 - antagonists & inhibitors; Receptor, ErbB-2 - biosynthesis; Simian virus 40; Transfection; Tumors
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-05-2109

Previously, we reported that SV40 T/t-common polypeptide, which contains the NH(2)-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-X(L), 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.