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Title: Role of thioredoxin reductase 1 and thioredoxin interacting protein in prognosis of breast cancer
Authors: Cadenas, CristinaFranckenstein, DennisSchmidt, MarcusGehrmann, MathiasHermes, MatthiasGeppert, BettinaSchormann, WiebkeMaccoux, Lindsey J.Schug, MarkusSchumann, AnikaWilhelm, ChristianFreis, EvgeniaIckstadt, KatjaRahnenführer, JörgBaumbach, Jörg I.Sickmann, AlbertHengstler, Jan G.
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Issue Date: 2010
Published in: Breast Cancer Research, Volume 12, Issue 3
Publisher: London : BioMed Central
Abstract: Introduction: The purpose of this work was to study the prognostic influence in breast cancer of thioredoxin reductase 1 (TXNRD1) and thioredoxin interacting protein (TXNIP), key players in oxidative stress control that are currently evaluated as possible therapeutic targets. Methods: Analysis of the association of TXNRD1 and TXNIP RNA expression with the metastasis-free interval (MFI) was performed in 788 patients with node-negative breast cancer, consisting of three individual cohorts (Mainz, Rotterdam and Transbig). Correlation with metagenes and conventional clinical parameters (age, pT stage, grading, hormone and ERBB2 status) was explored. MCF-7 cells with a doxycycline-inducible expression of an oncogenic ERBB2 were used to investigate the influence of ERBB2 on TXNRD1 and TXNIP transcription. Results: TXNRD1 was associated with worse MFI in the combined cohort (hazard ratio = 1.955; P < 0.001) as well as in all three individual cohorts. In contrast, TXNIP was associated with better prognosis (hazard ratio = 0.642; P < 0.001) and similar results were obtained in all three subcohorts. Interestingly, patients with ERBB2-status-positive tumors expressed higher levels of TXNRD1. Induction of ERBB2 in MCF-7 cells caused not only an immediate increase in TXNRD1 but also a strong decrease in TXNIP. A subsequent upregulation of TXNIP as cells undergo senescence was accompanied by a strong increase in levels of reactive oxygen species. Conclusions: TXNRD1 and TXNIP are associated with prognosis in breast cancer, and ERBB2 seems to be one of the factors shifting balances of both factors of the redox control system in a prognostic unfavorable manner.
Keywords: Apoptosis Signal Regulate Kinase; TXNIP Expression; ERBB2 Status; Oncogenic ERBB2; NeuT Cell
DDC: 610
License: CC BY 2.0 Unported
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