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 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.
Hashiguchi
Koichi
K
Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Nishi-cho 86, Yonago 683-8504, Japan.
Tsuchiya
Hiroyuki
H
Tomita
Akiko
A
Ueda
Chisa
C
Akechi
Yuji
Y
Sakabe
Tomohiko
T
Kurimasa
Akihiro
A
Nozaki
Masami
M
Yamada
Toshiyuki
T
Tsuchida
Shigeki
S
Shiota
Goshi
G
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism*; D012176:Retinoids / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
D000970:Antineoplastic Agents; C099555:CD 437; D002352:Carrier Proteins; C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D012176:Retinoids; C486715:TXNIP protein, human