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

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

Biochemical and biophysical research communications, 2008-10, Vol.375 (4), p.614-618 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
An N-terminal 78 amino acid truncation of REIC/Dkk-3 effectively induces apoptosis
Autor: Abarzua, Fernando ; Kashiwakura, Yuji ; Takaoka, Munenori ; Watanabe, Masami ; Ochiai, Kazuhiko ; Sakaguchi, Masakiyo ; Iwawaki, Takao ; Tanimoto, Ryuta ; Nasu, Yasutomo ; Huh, Nam-ho ; Kumon, Hiromi
Assuntos: Amino Acid Sequence ; Animals ; Apoptosis ; Cationic biodegradable polymer ; Cell Line, Tumor ; Endoplasmic Reticulum - metabolism ; ER stress ; Gene therapy ; Genes, Tumor Suppressor ; Genetic Therapy ; Humans ; Intercellular Signaling Peptides and Proteins - genetics ; Male ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Polymers - chemistry ; Prostatic Neoplasms - therapy ; REIC/Dkk-3 ; Sequence Deletion ; Transfection - methods ; Truncation form ; Xenograft Model Antitumor Assays
É parte de: Biochemical and biophysical research communications, 2008-10, Vol.375 (4), p.614-618
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: 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.
Editor: United States: Elsevier Inc
Idioma: Inglês

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

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

United States: Elsevier Inc

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