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. 1998 Dec;89(12):1326–1333. doi: 10.1111/j.1349-7006.1998.tb00530.x

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 1,2, Akihiro Umezawa 1, Atsushi Suzuki 1, Hajime Okita 1, Makoto Sano 1, Yoshiki Hiraoka 3, Sadakazu Aiso 3, Takao Saruta 2, Jun‐ichi Hata 1,✉
PMCID: PMC5921739  PMID: 10081494

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 chemo‐therapeutic 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.

Keywords: mcl‐1/EAT, Apoptosis, cis‐Diammine dichloroplatinum (II), bcl‐2, p53

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