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

被引:13
作者
Ando, T
Umezawa, A
Suzuki, A
Okita, H
Sano, M
Hiraoka, Y
Aiso, S
Saruta, T
Hata, J
机构
[1] Keio Univ, Sch Med, Dept Pathol, Shinjuku Ku, Tokyo 1608582, Japan
[2] Keio Univ, Sch Med, Dept Internal Med, Shinjuku Ku, Tokyo 1608582, Japan
[3] Keio Univ, Sch Med, Dept Anat, Shinjuku Ku, Tokyo 1608582, Japan
来源
JAPANESE JOURNAL OF CANCER RESEARCH | 1998年 / 89卷 / 12期
关键词
mcl-1/EAT; apoptosis; cis-diammine dichloroplatinum (II); bcl-2; p53;
D O I
10.1111/j.1349-7006.1998.tb00530.x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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/mlc-1 was capable of delaying the onset of p53-independent apoptosis, although it could not inhibit apoptosis completely. Since CDDP and carboplatin damage DIVA and then activate c-abl and the JNK/SAPK pathway, EAT/mcl-1 mag 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.
引用
收藏
页码:1326 / 1333
页数:8
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