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

研究成果: Article査読

11 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1326-1333
ページ数8
ジャーナルJapanese Journal of Cancer Research
89
12
DOI
出版ステータスPublished - 1998
外部発表はい

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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