Gene therapy for human small-cell lung carcinoma by inactivation of Skp-2 with virally mediated RNA interference

H. Sumimoto; S. Yamagata; A. Shimizu; H. Miyoshi; H. Mizuguchi; T. Hayakawa; M. Miyagishi; K. Taira; Y. Kawakami

doi:10.1038/sj.gt.3302391

Gene therapy for human small-cell lung carcinoma by inactivation of Skp-2 with virally mediated RNA interference

H. Sumimoto, S. Yamagata, A. Shimizu, H. Miyoshi, H. Mizuguchi, T. Hayakawa, M. Miyagishi, K. Taira, Y. Kawakami

Research output: Contribution to journal › Article › peer-review

78 Citations (Scopus)

Abstract

Increase of Skp-2, which is involved in the degradation of cell cycle regulators including p27^Kip1, p21 and c-myc, is one of the important mechanisms for dysregulation of cell cycles in various cancers. We applied RNA interference (RNAi) for Skp-2 by using HIV-lentiviral or adenoviral vectors for a human small-cell lung carcinoma cell line with increased Skp-2 to evaluate RNAi strategy for cancer gene therapy. HIV-lentivirus-mediated RNAi for Skp-2 resulted in efficient inhibition of the in vitro cell growth of cancer cells with increased Skp-2 through the increase of p27^Kip1 and p21, but no significant effect on the growth of cells without high Skp-2 expression. Furthermore, intratumoral administration of adenovirus siRNA vector for Skp-2 efficiently inhibited growth of established subcutaneous tumor on NOD/SCID mice. These results indicate that the Skp-2 RNAi may be a useful strategy for gene therapy of cancers with high Skp-2 expression.

Original language	English
Pages (from-to)	95-100
Number of pages	6
Journal	Gene Therapy
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/sj.gt.3302391
Publication status	Published - 2005 Jan
Externally published	Yes

Keywords

Adenovirus
Lentivirus
RNA interference
Skp-2

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/sj.gt.3302391

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title = "Gene therapy for human small-cell lung carcinoma by inactivation of Skp-2 with virally mediated RNA interference",

abstract = "Increase of Skp-2, which is involved in the degradation of cell cycle regulators including p27Kip1, p21 and c-myc, is one of the important mechanisms for dysregulation of cell cycles in various cancers. We applied RNA interference (RNAi) for Skp-2 by using HIV-lentiviral or adenoviral vectors for a human small-cell lung carcinoma cell line with increased Skp-2 to evaluate RNAi strategy for cancer gene therapy. HIV-lentivirus-mediated RNAi for Skp-2 resulted in efficient inhibition of the in vitro cell growth of cancer cells with increased Skp-2 through the increase of p27Kip1 and p21, but no significant effect on the growth of cells without high Skp-2 expression. Furthermore, intratumoral administration of adenovirus siRNA vector for Skp-2 efficiently inhibited growth of established subcutaneous tumor on NOD/SCID mice. These results indicate that the Skp-2 RNAi may be a useful strategy for gene therapy of cancers with high Skp-2 expression.",

keywords = "Adenovirus, Lentivirus, RNA interference, Skp-2",

author = "H. Sumimoto and S. Yamagata and A. Shimizu and H. Miyoshi and H. Mizuguchi and T. Hayakawa and M. Miyagishi and K. Taira and Y. Kawakami",

note = "Funding Information: We thank Dr M Matsuoka for his helpful discussion and critical review of our manuscript. This work was supported in part by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, a grant-in-aid for Cancer Research from the Ministry of Health, Labour and Welfare, Japan, for Second Term Comprehensive 10-year Strategy for Cancer Control, the Science Research Promotion Fund from the Promotion and Mutual Aid Cooperation for Private Schools for Japan, and the Keio Gijuku Academic Development Funds.",

year = "2005",

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doi = "10.1038/sj.gt.3302391",

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journal = "Gene Therapy",

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AU - Sumimoto, H.

AU - Yamagata, S.

AU - Shimizu, A.

AU - Miyoshi, H.

AU - Mizuguchi, H.

AU - Hayakawa, T.

AU - Miyagishi, M.

AU - Taira, K.

AU - Kawakami, Y.

N1 - Funding Information: We thank Dr M Matsuoka for his helpful discussion and critical review of our manuscript. This work was supported in part by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, a grant-in-aid for Cancer Research from the Ministry of Health, Labour and Welfare, Japan, for Second Term Comprehensive 10-year Strategy for Cancer Control, the Science Research Promotion Fund from the Promotion and Mutual Aid Cooperation for Private Schools for Japan, and the Keio Gijuku Academic Development Funds.

PY - 2005/1

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N2 - Increase of Skp-2, which is involved in the degradation of cell cycle regulators including p27Kip1, p21 and c-myc, is one of the important mechanisms for dysregulation of cell cycles in various cancers. We applied RNA interference (RNAi) for Skp-2 by using HIV-lentiviral or adenoviral vectors for a human small-cell lung carcinoma cell line with increased Skp-2 to evaluate RNAi strategy for cancer gene therapy. HIV-lentivirus-mediated RNAi for Skp-2 resulted in efficient inhibition of the in vitro cell growth of cancer cells with increased Skp-2 through the increase of p27Kip1 and p21, but no significant effect on the growth of cells without high Skp-2 expression. Furthermore, intratumoral administration of adenovirus siRNA vector for Skp-2 efficiently inhibited growth of established subcutaneous tumor on NOD/SCID mice. These results indicate that the Skp-2 RNAi may be a useful strategy for gene therapy of cancers with high Skp-2 expression.

AB - Increase of Skp-2, which is involved in the degradation of cell cycle regulators including p27Kip1, p21 and c-myc, is one of the important mechanisms for dysregulation of cell cycles in various cancers. We applied RNA interference (RNAi) for Skp-2 by using HIV-lentiviral or adenoviral vectors for a human small-cell lung carcinoma cell line with increased Skp-2 to evaluate RNAi strategy for cancer gene therapy. HIV-lentivirus-mediated RNAi for Skp-2 resulted in efficient inhibition of the in vitro cell growth of cancer cells with increased Skp-2 through the increase of p27Kip1 and p21, but no significant effect on the growth of cells without high Skp-2 expression. Furthermore, intratumoral administration of adenovirus siRNA vector for Skp-2 efficiently inhibited growth of established subcutaneous tumor on NOD/SCID mice. These results indicate that the Skp-2 RNAi may be a useful strategy for gene therapy of cancers with high Skp-2 expression.

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Gene therapy for human small-cell lung carcinoma by inactivation of Skp-2 with virally mediated RNA interference

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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