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 ((1-78)REIC/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 (1-78)REIC/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.
authors: Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Shikata 2-5-1, Okayama 700-8558, Japan.
authors: Fernando
authors: F
authors: Abarzua
authors: Yuji
authors: Y
authors: Kashiwakura
authors: Munenori
authors: M
authors: Takaoka
authors: Masami
authors: M
authors: Watanabe
authors: Kazuhiko
authors: K
authors: Ochiai
authors: Masakiyo
authors: M
authors: Sakaguchi
authors: Takao
authors: T
authors: Iwawaki
authors: Ryuta
authors: R
authors: Tanimoto
authors: Yasutomo
authors: Y
authors: Nasu
authors: Nam-Ho
authors: NH
authors: Huh
authors: Hiromi
authors: H
authors: Kumon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D018925:Chemokines; D004721:Endoplasmic Reticulum / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011108:Polymers / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000628:therapy*; D017384:Sequence Deletion; D014162:Transfection / Q000379:methods; D023041:Xenograft Model Antitumor Assays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D011108:Polymers