Involvement of ETS1 in thioredoxin-binding protein 2 transcription induced by a synthetic retinoid CD437 in human osteosarcoma cells

CD437, a synthetic retinoid, has a potent antitumor activity, in which an RAR-independent mechanism may be involved. Our previous study showed that CD437 transcriptionally upregulates the expression of thioredoxin-binding protein 2 (TBP2), leading to c-Jun N-terminal kinase 1 (JNK1)-mediated apoptos...

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Published in:Biochemical and biophysical research communications 2010-01, Vol.391 (1), p.621-626
Main Authors: Hashiguchi, Koichi, Tsuchiya, Hiroyuki, Tomita, Akiko, Ueda, Chisa, Akechi, Yuji, Sakabe, Tomohiko, Kurimasa, Akihiro, Nozaki, Masami, Yamada, Toshiyuki, Tsuchida, Shigeki, Shiota, Goshi
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Apoptosis
Carrier Proteins - genetics
CD437
Cell Line, Tumor
Chromatin Immunoprecipitation
ETS1
Humans
Neoplasms - metabolism
Osteosarcoma
Promoter Regions, Genetic
Proto-Oncogene Protein c-ets-1 - metabolism
Retinoids - pharmacology
Synthetic retinoid
Thioredoxin-binding protein 2
Transcription, Genetic - drug effects
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Summary:CD437, a synthetic retinoid, has a potent antitumor activity, in which an RAR-independent mechanism may be involved. Our previous study showed that CD437 transcriptionally upregulates the expression of thioredoxin-binding protein 2 (TBP2), leading to c-Jun N-terminal kinase 1 (JNK1)-mediated apoptosis. In the present study, we addressed the mechanism, by which CD437 induces TBP2 mRNA expression. CD437 efficiently caused the cell death of human osteosarcoma cells via apoptosis. CD437 also induced JNK1 activation through the upregulation of TBP2 mRNA, in consistent with our previous observation. A luciferase reporter assay for TBP2 promoter activation suggested that CD437-regulated TBP2 mRNA transcription requires the region between −400 and −300, which contains multiple possible ETS-binding sites. Finally, we demonstrated CD437-dependent recruitment of ETS1 transcription factor to this region by chromatin immunoprecipitation assay. These data suggest that ETS1 is involved in CD437-induced TBP2 mRNA expression in human osteosarcoma MG-63 cells.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2009.11.109