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RRR‐α‐tocopheryl succinate induction of prolonged activation of c‐jun amino‐terminal kinase and c‐jun during induction of apoptosis in human MDA‐MB‐435 breast cancer cells
Author(s) -
Yu Weiping,
SimmonsMenchaca Marla,
You Huihong,
Brown Powel,
Birrer Michael J.,
Sanders Bob G.,
Kline Kimberly
Publication year - 1998
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(199808)22:4<247::aid-mc6>3.0.co;2-g
Subject(s) - biology , c jun , transactivation , microbiology and biotechnology , activator (genetics) , apoptosis , luciferase , transfection , kinase , gene expression , transcription factor , receptor , gene , biochemistry
We have demonstrated that RRR‐α‐tocopheryl succinate (10 μg/mL vitamin E succinate (VES) treatment of estrogen receptor–negative MDA‐MB‐435 human breast cancer cells induces 9, 19, 51, and 72% apoptotic cells on days 1–4, respectively, after treatment, which involves transforming growth factor‐β signaling. Here, we show that VES‐triggered apoptosis of MDA‐MB‐435 cells induced prolonged elevated expression of c‐ jun mRNA and protein (neither of which was caused by major increases in stability) and also induced enhanced activator protein‐1 (AP‐1) binding to the consensus DNA oligomer. Furthermore, VES treatments resulted in increased AP‐1 transactivation activity, as measured with an AP‐1 promoter/luciferase reporter construct and by the measurement of increased mRNA expression of the AP‐1–dependent endogenous gene collagenase. Evidence of VES‐induced involvement of the c‐jun amino‐terminal kinase in these AP‐1–dependent events was suggested by data showing prolonged activity of this kinase, as measured by a kinase assay using glutathione S‐transferase–c‐jun as the substrate. The c‐jun–dependent transcriptional activity was verified by cotransfection of a chimeric transcription factor having a galactose 4 DNA‐binding domain coupled with the transactivation domain of c‐jun plus the reporter plasmid 5X GAL4‐luciferase. MDA‐MB‐435 cells infected with an adenovirus expression vector containing the TAM‐67 sequence for dominant/negative‐acting mutant c‐jun or transiently transfected with c‐ jun antisense exhibited a 50–77% reduction in VES‐mediated apoptosis as compared with control adenovirus‐infected or control sense oligomer–transfected cells. Mol. Carcinog. 22:247–257, 1998. © 1998 Wiley‐Liss, Inc.