An N-terminal 78 amino acid truncation of REIC/Dkk-3 effectively induces apoptosis

Fernando Abarzua; Yuji Kashiwakura; Munenori Takaoka; Masami Watanabe; Kazuhiko Ochiai; Masakiyo Sakaguchi; Takao Iwawaki; Ryuta Tanimoto; Yasutomo Nasu; Nam ho Huh; Hiromi Kumon

doi:10.1016/j.bbrc.2008.08.079

An N-terminal 78 amino acid truncation of REIC/Dkk-3 effectively induces apoptosis

Fernando Abarzua, Yuji Kashiwakura, Munenori Takaoka, Masami Watanabe, Kazuhiko Ochiai, Masakiyo Sakaguchi, Takao Iwawaki, Ryuta Tanimoto, Yasutomo Nasu, Nam ho Huh, Hiromi Kumon

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Abstract

Overexpression of REIC/Dkk-3 (a tumor suppressor gene) induces cancer cell apoptosis through endoplasmic reticulum (ER) stress. Therefore, the identification of the portion of REIC/Dkk-3 that causes ER stress may be essential for the development of cancer treatment based on REIC/Dkk-3. Here, we made several truncated forms of REIC/Dkk-3 and investigated their therapeutic potentials against prostate cancer. Among three truncated forms, a variant comprising the N-terminal 78 amino acid region of REIC/Dkk-3 (^1-78REIC/Dkk-3) most strongly induced ER stress and apoptosis in human prostate cancer cells (PC3). For in vivo gene expression, we coupled a biodegradable polymer with naked DNA, which attained robust trans-gene expression in PC3-derived subcutaneous tumor. In therapeutic experiments, we demonstrated that multiple direct injections of polymer-conjugated ^1-78REIC/Dkk-3 plasmid provoke ER stress and significantly reduced the subcutaneous tumor volume compared with the control group. We suggest this non-viral strategy may be an effective alternative to viral gene therapy.

Original language	English
Pages (from-to)	614-618
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	375
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2008.08.079
Publication status	Published - Oct 31 2008

Keywords

Cationic biodegradable polymer
ER stress
Gene therapy
REIC/Dkk-3
Truncation form

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

UN SDGs

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

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10.1016/j.bbrc.2008.08.079

Cite this

@article{eb63338fd0ea4c3e80dcca08e4ba300b,

title = "An N-terminal 78 amino acid truncation of REIC/Dkk-3 effectively induces apoptosis",

abstract = "Overexpression of REIC/Dkk-3 (a tumor suppressor gene) induces cancer cell apoptosis through endoplasmic reticulum (ER) stress. Therefore, the identification of the portion of REIC/Dkk-3 that causes ER stress may be essential for the development of cancer treatment based on REIC/Dkk-3. Here, we made several truncated forms of REIC/Dkk-3 and investigated their therapeutic potentials against prostate cancer. Among three truncated forms, a variant comprising the N-terminal 78 amino acid region of REIC/Dkk-3 (1-78REIC/Dkk-3) most strongly induced ER stress and apoptosis in human prostate cancer cells (PC3). For in vivo gene expression, we coupled a biodegradable polymer with naked DNA, which attained robust trans-gene expression in PC3-derived subcutaneous tumor. In therapeutic experiments, we demonstrated that multiple direct injections of polymer-conjugated 1-78REIC/Dkk-3 plasmid provoke ER stress and significantly reduced the subcutaneous tumor volume compared with the control group. We suggest this non-viral strategy may be an effective alternative to viral gene therapy.",

keywords = "Cationic biodegradable polymer, ER stress, Gene therapy, REIC/Dkk-3, Truncation form",

author = "Fernando Abarzua and Yuji Kashiwakura and Munenori Takaoka and Masami Watanabe and Kazuhiko Ochiai and Masakiyo Sakaguchi and Takao Iwawaki and Ryuta Tanimoto and Yasutomo Nasu and Huh, {Nam ho} and Hiromi Kumon",

note = "Funding Information: This work was also supported by Grant-in-Aid for JSPS Postdoctoral Fellowship for Foreign Research number: P 07213. Funding Information: This research was supported by Special Coordination Funds for Promoting Science and Technology: [Formation of Innovation Center for Fusion of Advanced Technologies] from the Japan Ministry of Education, Culture, Sports, Science, and Technology. ",

year = "2008",

month = oct,

day = "31",

doi = "10.1016/j.bbrc.2008.08.079",

language = "English",

volume = "375",

pages = "614--618",

journal = "Biochemical and Biophysical Research Communications",

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T1 - An N-terminal 78 amino acid truncation of REIC/Dkk-3 effectively induces apoptosis

AU - Abarzua, Fernando

AU - Kashiwakura, Yuji

AU - Takaoka, Munenori

AU - Watanabe, Masami

AU - Ochiai, Kazuhiko

AU - Sakaguchi, Masakiyo

AU - Iwawaki, Takao

AU - Tanimoto, Ryuta

AU - Nasu, Yasutomo

AU - Huh, Nam ho

AU - Kumon, Hiromi

N1 - Funding Information: This work was also supported by Grant-in-Aid for JSPS Postdoctoral Fellowship for Foreign Research number: P 07213. Funding Information: This research was supported by Special Coordination Funds for Promoting Science and Technology: [Formation of Innovation Center for Fusion of Advanced Technologies] from the Japan Ministry of Education, Culture, Sports, Science, and Technology.

PY - 2008/10/31

Y1 - 2008/10/31

N2 - Overexpression of REIC/Dkk-3 (a tumor suppressor gene) induces cancer cell apoptosis through endoplasmic reticulum (ER) stress. Therefore, the identification of the portion of REIC/Dkk-3 that causes ER stress may be essential for the development of cancer treatment based on REIC/Dkk-3. Here, we made several truncated forms of REIC/Dkk-3 and investigated their therapeutic potentials against prostate cancer. Among three truncated forms, a variant comprising the N-terminal 78 amino acid region of REIC/Dkk-3 (1-78REIC/Dkk-3) most strongly induced ER stress and apoptosis in human prostate cancer cells (PC3). For in vivo gene expression, we coupled a biodegradable polymer with naked DNA, which attained robust trans-gene expression in PC3-derived subcutaneous tumor. In therapeutic experiments, we demonstrated that multiple direct injections of polymer-conjugated 1-78REIC/Dkk-3 plasmid provoke ER stress and significantly reduced the subcutaneous tumor volume compared with the control group. We suggest this non-viral strategy may be an effective alternative to viral gene therapy.

AB - Overexpression of REIC/Dkk-3 (a tumor suppressor gene) induces cancer cell apoptosis through endoplasmic reticulum (ER) stress. Therefore, the identification of the portion of REIC/Dkk-3 that causes ER stress may be essential for the development of cancer treatment based on REIC/Dkk-3. Here, we made several truncated forms of REIC/Dkk-3 and investigated their therapeutic potentials against prostate cancer. Among three truncated forms, a variant comprising the N-terminal 78 amino acid region of REIC/Dkk-3 (1-78REIC/Dkk-3) most strongly induced ER stress and apoptosis in human prostate cancer cells (PC3). For in vivo gene expression, we coupled a biodegradable polymer with naked DNA, which attained robust trans-gene expression in PC3-derived subcutaneous tumor. In therapeutic experiments, we demonstrated that multiple direct injections of polymer-conjugated 1-78REIC/Dkk-3 plasmid provoke ER stress and significantly reduced the subcutaneous tumor volume compared with the control group. We suggest this non-viral strategy may be an effective alternative to viral gene therapy.

KW - Cationic biodegradable polymer

KW - ER stress

KW - Gene therapy

KW - REIC/Dkk-3

KW - Truncation form

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ER -

An N-terminal 78 amino acid truncation of REIC/Dkk-3 effectively induces apoptosis

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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