Mechanistic analysis of resistance to REIC/Dkk-3-induced apoptosis in human bladder cancer cells

Tomoko Kobayashi, Masakiyo Sakaguchi, Ryuta Tanimoto, Fernando Abarzua, Mikiro Takaishi, Haruki Kaku, Ken Kataoka, Takashi Saika, Yasutomo Nasu, Masahiro Miyazaki, Hiromi Kumon, Nam Ho Huh

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We have recently shown that a new therapeutic modality using the REIC/Dkk-3 gene (Ad-REIC) is effective against various human cancers, including those of prostate, testis and breast origins. The aim of the present study was to examine the sensitivity of bladder cancers to Ad-REIC and to clarify the molecular mechanisms that determine sensitivity/resistance. We found that 2 human bladder cancer cell lines, T24 and J82, are resistant to Ad-REIC. In T24 and J82 cells, the ER stress response and activation of JNK were observed in a manner similar to that in the sensitive PC3 cells. Translocation of Bax to mitochondria occurred in PC3 cells but not in T24 and J82 cells. Bcl-2 was remarkably overexpressed in T24 and J82 compared with the expression levels in sensitive cell lines. Treatment of T24 and J82 cells with a Bcl-2 inhibitor sensitized the cells to Ad-REIC-induced apoptosis. The results indicate that some human bladder cancers are resistant to apoptosis induced by overexpression of REIC/Dkk-3, which is at least in part due to up-regulation of Bcl-2. These results provide a basis for possible use of Bcl-2 as a marker of sensitive cancers and to try to sensitize resistant cancers to Ad-REIC by down-regulation of Bcl-2. Copyright

Original languageEnglish
Article number6
JournalActa medica Okayama
Volume62
Issue number6
Publication statusPublished - Dec 2008

Keywords

  • Apoptosis
  • Bcl-2
  • Bladder cancer
  • REIC/Dkk-3

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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