In vitro and in vivo growth suppression of human papillomavirus 16-positive cervical cancer cells by E6 siRNA

Mitsuo Yoshinouchi; Taketo Yamada; Masahiro Kizaki; Jin Fen; Takeyoshi Koseki; Yasuo Ikeda; Tatsuji Nishihara; Kenji Yamato

doi:10.1016/j.ymthe.2003.08.004

In vitro and in vivo growth suppression of human papillomavirus 16-positive cervical cancer cells by E6 siRNA

Mitsuo Yoshinouchi, Taketo Yamada, Masahiro Kizaki, Jin Fen, Takeyoshi Koseki, Yasuo Ikeda, Tatsuji Nishihara, Kenji Yamato

Department of Pathology

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

177 Citations (Scopus)

Abstract

Human papillomavirus type 16 (HPV16), a causative agent of cervical cancers, encodes the E6 and E7 oncogenes, whose simultaneous expression is pivotal for 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 on the cell growth of HPV16-related cervical cancer cells. Using SiHa cervical cancer cells, we demonstrated that E6 siRNA decreased the levels of mRNA encoding E6 as well as that encoding 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. Further, SiHa cells treated with E6 siRNA formed tumors in NOD/SCID mice that were significantly smaller than in those treated with control siRNA. Our results show HPV E6 siRNA as a candidate for gene-specific therapy for HPV-related cervical cancer.

Original language	English
Pages (from-to)	762-768
Number of pages	7
Journal	Molecular Therapy
Volume	8
Issue number	5
DOIs	https://doi.org/10.1016/j.ymthe.2003.08.004
Publication status	Published - 2003 Nov

Keywords

Cell growth
E6
E7
HPV16
NOD/SCID mouse
RNAi
Rb
Tumor formation
p53
siRNA

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Genetics
Pharmacology
Drug Discovery

UN SDGs

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

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10.1016/j.ymthe.2003.08.004

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title = "In vitro and in vivo growth suppression of human papillomavirus 16-positive cervical cancer cells by E6 siRNA",

abstract = "Human papillomavirus type 16 (HPV16), a causative agent of cervical cancers, encodes the E6 and E7 oncogenes, whose simultaneous expression is pivotal for 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 on the cell growth of HPV16-related cervical cancer cells. Using SiHa cervical cancer cells, we demonstrated that E6 siRNA decreased the levels of mRNA encoding E6 as well as that encoding 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 p21CIP1/WAF1 induction and hypophosphorylation of retinoblastoma protein. Further, SiHa cells treated with E6 siRNA formed tumors in NOD/SCID mice that were significantly smaller than in those treated with control siRNA. Our results show HPV E6 siRNA as a candidate for gene-specific therapy for HPV-related cervical cancer.",

keywords = "Cell growth, E6, E7, HPV16, NOD/SCID mouse, RNAi, Rb, Tumor formation, p53, siRNA",

author = "Mitsuo Yoshinouchi and Taketo Yamada and Masahiro Kizaki and Jin Fen and Takeyoshi Koseki and Yasuo Ikeda and Tatsuji Nishihara and Kenji Yamato",

note = "Funding Information: This work was supported in part by grants-in-aid for Scientific Research (C) from the Japan Society for the Promotion of Science [15591749 (M.Y.), 15591991 (K.Y.)]",

year = "2003",

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doi = "10.1016/j.ymthe.2003.08.004",

language = "English",

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pages = "762--768",

journal = "Molecular Therapy",

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T1 - In vitro and in vivo growth suppression of human papillomavirus 16-positive cervical cancer cells by E6 siRNA

AU - Yoshinouchi, Mitsuo

AU - Yamada, Taketo

AU - Kizaki, Masahiro

AU - Fen, Jin

AU - Koseki, Takeyoshi

AU - Ikeda, Yasuo

AU - Nishihara, Tatsuji

AU - Yamato, Kenji

N1 - Funding Information: This work was supported in part by grants-in-aid for Scientific Research (C) from the Japan Society for the Promotion of Science [15591749 (M.Y.), 15591991 (K.Y.)]

PY - 2003/11

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N2 - Human papillomavirus type 16 (HPV16), a causative agent of cervical cancers, encodes the E6 and E7 oncogenes, whose simultaneous expression is pivotal for 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 on the cell growth of HPV16-related cervical cancer cells. Using SiHa cervical cancer cells, we demonstrated that E6 siRNA decreased the levels of mRNA encoding E6 as well as that encoding 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 p21CIP1/WAF1 induction and hypophosphorylation of retinoblastoma protein. Further, SiHa cells treated with E6 siRNA formed tumors in NOD/SCID mice that were significantly smaller than in those treated with control siRNA. Our results show HPV E6 siRNA as a candidate for gene-specific therapy for HPV-related cervical cancer.

AB - Human papillomavirus type 16 (HPV16), a causative agent of cervical cancers, encodes the E6 and E7 oncogenes, whose simultaneous expression is pivotal for 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 on the cell growth of HPV16-related cervical cancer cells. Using SiHa cervical cancer cells, we demonstrated that E6 siRNA decreased the levels of mRNA encoding E6 as well as that encoding 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 p21CIP1/WAF1 induction and hypophosphorylation of retinoblastoma protein. Further, SiHa cells treated with E6 siRNA formed tumors in NOD/SCID mice that were significantly smaller than in those treated with control siRNA. Our results show HPV E6 siRNA as a candidate for gene-specific therapy for HPV-related cervical cancer.

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KW - E7

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KW - NOD/SCID mouse

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KW - Rb

KW - Tumor formation

KW - p53

KW - siRNA

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In vitro and in vivo growth suppression of human papillomavirus 16-positive cervical cancer cells by E6 siRNA

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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