Adenovirus-mediated overexpression of REIC/Dkk-3 selectively induces apoptosis in human prostate cancer cells through activation of c-Jun-NH 2-kinase

Fernando Abarzua, Masakiyo Sakaguchi, Mikiro Takaishi, Yasutomo Nasu, Kyouhei Kurose, Shin Ebara, Masahiro Miyazaki, Masayoshi Namba, Hiromi Kumon, Nam Ho Huh

Research output: Contribution to journalArticle

152 Citations (Scopus)

Abstract

Alteration in genes which takes place during malignant conversion and progression could be potential targets for gene therapy. We previously identified REIC/Dkk-3 as a gene whose expression is reduced in many human cancers. Here, we showed that expression of REIC/Dkk-3 was consistently reduced in human prostate cancer tissues in a stage-dependent manner. Forced expression of REIC/Dkk-3 induced apoptosis in human prostate cancer cell lines lacking endogenous REIC/Dkk-3 expression but not in REIC/Dkk-3-proficient normal prostate epithelial and stromal cells. The apoptosis involved c-Jun-NH 2-kinase activation, mitochondrial translocation of Bax, and reduction of Bcl-2. A single injection of an adenovirus vector carrying REIC/Dkk-3 showed a dramatic antitumor effect on a xenotransplanted human prostate cancer. Thus, REIC/Dkk-3 could be a novel target for gene-based therapy of prostate cancer.

Original languageEnglish
Pages (from-to)9617-9622
Number of pages6
JournalCancer Research
Volume65
Issue number21
DOIs
Publication statusPublished - Nov 1 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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