EAT/mcl-1, a member of the bcl-2 related genes, confers resistance to apoptosis induced by cis-diammine dichloroplatinum (II) via a p53-independent pathway

Takashi Ando, Akihiro Umezawa, Atsushi Suzuki, Hajime Okita, Makoto Sano, Yoshiki Hiraoka, Sadakazu Aiso, Takao Saruta, Jun Ichi Hata

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

EAT/mcl-1 showed increased expression during the differentiation of a multipotent human embryonic carcinoma cell line, NCR-G3, and of myeloblastic cells 'ML-1,' and has sequence similarity to Bcl-2. In this present study, we determined whether the apoptotic cell death induced by chemotherapeutic agents could be inhibited by EAT/mcl-1, as has been found with Bcl-2. Cells transfected with EAT/mcl-1 showed higher resistance to cis-diammine dichloroplatinum (II) (CDDP) and carboplatin compared with the parental line (10)1 and neomycin-resistance gene-transfected clone, (10)1/neo. There was, however, no difference in sensitivity to etoposide, N,N-bis-(2-chloroethyl)-N'-(3-hydroxypropyl) phosphordiamidic acid cyclic ester monohydrate, adriamycin or other chemotherapeutic agents tested. DNA fragmentation of the parental cells following treatment with CDDP and carboplatin was observed in a concentration-dependent manner. In contrast, cells transfected with EAT/mcl-1 did not show DNA fragmentation following treatment with the same concentration of these drugs. EAT/mcl-1 was capable of delaying the onset of p53-independent apoptosis, although it could not inhibit apoptosis completely. Since CDDP and carboplatin damage DNA and then activate c-abl and the JNK/SAPK pathway, EAT/mcl-1 may inhibit p53-independent apoptosis through a c-abl/JNK (SAPK)-dependent mechanism. EAT/mcl-1 has functional homology to Bcl-2 in that it can enhance cell viability under conditions which otherwise cause apoptosis and increase resistance to chemotherapeutic agents.

Original languageEnglish
Pages (from-to)1326-1333
Number of pages8
JournalJapanese Journal of Cancer Research
Volume89
Issue number12
DOIs
Publication statusPublished - 1998

Keywords

  • Apoptosis
  • bcl-2
  • cis-Diammine dichloroplatinum (II)
  • mcl-1/EAT
  • p53

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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