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The anti‐cancer drug cisplatin induces HSP25 in Ehrlich ascites tumor cells by a mechanism different from transcriptional stimulation influencing predominantly HSP25 translation
Author(s) -
Gotthardt Rainer,
Neininger Armin,
Gaestel Matthias
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960611)66:6<790::aid-ijc14>3.0.co;2-7
Subject(s) - cisplatin , heat shock protein , protein biosynthesis , messenger rna , gene expression , biology , microbiology and biotechnology , northern blot , transcription (linguistics) , hsp90 , chemistry , cancer research , gene , biochemistry , genetics , chemotherapy , linguistics , philosophy
Treatment of Ehrlich ascites tumor (EAT) cells with the anti‐cancer drug cisplatin induces an increase of the intracellular level of the small heat shock protein Hsp25 without stimulating the general stress response. The mechanism of this induction process was investigated at the levels of gene transcription, protein synthesis and stability. We show that an increased synthesis of Hsp25 is predominantly responsible for the increased intracellular level of this protein. In addition, there is a slightly increased metabolic stability of Hsp25 in cisplatin‐treated EAT cells. In contrast to the mechanism of Hsp25 induction by heat shock and other chemical stresses, stimulated synthesis of Hsp25 after treatment with cisplatin is not the result of increased transcription of the hsp 25 gene. Cisplatin treatment does not significantly influence the oligomerization of heat shock transcription factors 1 and 2, hsp 25 promoter activity or hsp 25 mRNA stability, as judged by cross‐linking experiments, reporter gene assay and Northern blot analysis. Hence, cisplatin specifically induces Hsp25 synthesis at the level of mRNA translation without any changes in hsp 25 gene transcription. © 1996 Wiley‐Liss, Inc.