2004 Fiscal Year Final Research Report Summary
In vitro and in vivo growth suppression of HPV-related cancer cells by siRNA targeting E6 oncogene
| Project/Area Number |
15591991
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathobiological dentistry/Dental radiology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
YAMATO Kenji Tokyo Medical and Dental University, Graduate School, Division of Oral Health Science, Lecturer, 大学院・医歯学総合研究科, 講師 (50174751)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Taketo Keio University, School of Medicine, Lecturer, 医学部, 講師 (60230463)
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| Project Period (FY) |
2003 – 2004
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| Keywords | HPV / E6 / RNAi / siRNA / growth |
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| Research Abstract |
Human papillomavirus (HPV) types 16 and 18, causative agents of cervical cancers, encode the E6 and E7 oncogenes, whose simultaneous expression is pivotal for the malignant transformation and maintenance of malignant phenotypes. In the hope of developing a gene-specific therapy for HPV-related cancer, we examined the effects of E6 short-interfering RNA (siRNA) on the expression of these oncogenes and cell growth of HPV-related cervical cancer cells. Using SiHa cervical cancer cells, we demonstrated that HPV16 E6 siRNA decreased the levels of mRNA coding E6 as well as that coding E7 protein, and also induced nuclear accumulation of p53, the most important target of E6. E6 siRNA suppressed monolayer and anchorage-independent growth of SiHa cells, which was associated with p21^<CIP1/WAF1> induction and hypophosphorylation of retinoblastoma protein (Rb). Further, SiHa cells treated with E6 siRNA formed tumors in NOD/SCID mice that were significantly smaller than in those treated with control siRNA.
we also found 2 types of siRNAs targeting HPV18 E6 which exerted a negative growth effect on HPV18-positive cervical cancer cells (HeLa and SW756), in part, inducing cell death. One siRNA (Ex-18E6) knocked down both E6 and E7 expression. The other (Sp-18E6) suppressed E6 to a similar level as Ex-18E6, however, less efficiently inhibited E7 as compared to Ex-18E6. Although both siRNAs induced cell death, Sp-18E6 siRNA induced more prominent cell death than Ex-18E6, suggesting that selective knock-down of E6 might be superior to simultaneous knock-down of E6 and E7 for the siRNA therapy of cervical cancer.
Our results show HPV E6 siRNA as a candidate for gene-specific therapy for HPV-related cervical cancer.
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[Journal Article] Induction of apoptosis in leukemic cells by homovanillic acid derivative, capsaicin, through oxidative stress : implication of phosphorylation of p53 at Ser-15 residue by reactive oxygen species.2004
Author(s)
Ito, K., Nakazato, T., Yamato, K., Miyakawa, Y., Yamada, T.,, Hozumi, N., Segawa, K., Ikeda, Y., Kizaki, M.
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Journal Title
Cancer Res. 64
Pages: 1071-1078
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Induction of apoptosis in human myeloid leukemia cells by 1'-acetoxychavicol acetate (ACA) through a mitochondrial-and Fas-mediated dual mechanism.2004
Author(s)
Ito, K., Nakazawa, T., Murakami, A., Yamato, K., Miyakawa, Y., Yamada, T., Hozumi, N., Ohigashi, H., Ikeda, Y., Kizaki, M.
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Journal Title
Clinical Cancer Res. 10
Pages: 2120-2130
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Eradication of HPV post-surgical treatments, its correlation with specific types, types of surgery and the physical status.2004
Author(s)
Fen, J., Yoshinouchi, M., Nakamura.K., Kodama, J., Nasu, Y., Yamato, K., Hiramatsu, Y.
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Journal Title
Oncol.Rep. 12
Pages: 375-379
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Caffeine induces G2/M arrest and apoptosis via novel p53-dependent pathway in NB4 promonocytic leukemia cells.2003
Author(s)
Ito, K., Nakazoto, T., Miyakawa, Y., Yamato, K., Ikeda, Y., Kizaki, M.
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Journal Title
J.cell.Physiol. 196
Pages: 276-283
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] In vitro and in vivo growth suppression of human papillomavirus (HPV)16-positive cervical cancer cells by E6 siRNA.2003
Author(s)
Yoshinouchi, M., Yamada, T., Kizaki, M., Fen, J., Koseki, T., Ikeda, Y., Nishihara, T., Yamato, K.
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Journal Title
Mol.Ther. 8
Pages: 762-768
Description
「研究成果報告書概要(欧文)」より
