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This Article Accepted manuscript (PDF) All Versions of this Article: JME-08-0118v1 42/3/249    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Trojanowicz, B. Articles by Hoang-Vu, C. Search for Related Content PubMed PubMed Citation Articles by Trojanowicz, B. Articles by Hoang-Vu, C.

B Trojanowicz, Universitaesklinik und Poliklinik fuer Allgemein-, Viszeral- und Gefaesschirurgie, Martin-Luther Universitaet, Halle, Halle/Saale, Germany
A Winkler, Halle/Saale, Germany
K Hammje, Halle/Saale, Germany
Z Chen, Halle/Saale, Germany
C Sekulla, Halle/Saale, Germany
D Glanz, Institut fuer Physiologische Chemie, Martin-Luther Universitaet, Halle, Halle/Saale, Germany
C Schmutzler, Institut fuer Experimentelle Endokrinologie, Charite, Universitaetsmedizin Berlin, Berlin, Germany
B Mentrup, Orthopedic Center for Musculoskeletal Research, University of Wuerzburg, Wuerzburg, Germany
S Hombach-Klonisch, Department of Human Anatomy & Cell Science, University of Manitoba, Winnipeg, Manitoba, Winnipeg, Canada
T Klonisch, Winnipeg, Canada
R Finke, Universitaesklinik und Poliklinik fuer Kinderchirurgie, Martin-Luther Universitaet, Halle, Halle/Saale, Germany
J Koehrle, Berlin, Germany
H Dralle, Halle/Saale, Germany
C Hoang-Vu, Universitaesklinik und Poliklinik fuer Allgemein-, Viszeral- und Gefaesschirurgie, Martin-Luther Universitaet, Halle, Halle, Germany

Correspondence: Bogusz Trojanowicz, Email: bogusz.trojanowicz{at}medizin.uni-halle.de

Abstract

Retinoic acid (RA) acts as an anti-proliferative and re-differentiation agent in the therapy of thyroid carcinoma. Our previous studies demonstrated that pre-treatment of follicular thyroid carcinoma cell lines FTC-133 and FTC-238 resulted in decreased in-vitro proliferation rates and reduced tumor cell growth of xenotransplants. In addition to previous results we found that RA led to decreased vitality and invasiveness of FTC-133 and FTC-238 cells as they reacted with reduction of intracellular ATP levels and number of migrated cells, respectively. However the molecular mechanisms by which RA mediates these effects are not well understood. Two dimensional screening of the proteins related to ATP metabolism and western blot analysis revealed alpha-enolase (ENO1) to be down-regulated in FTC-133 and FTC-238 cells after RA treatment. Two-dimensional gel detection and mass spectrometric analysis revealed that ENO1 existed as three separate protein spots of distinct isoelectric points (ENO1-A1-A3). Comparative 2D gel analysis of fluorescently labelled protein samples of RA treated and untreated FTC-133 (DIGE) demonstrated a selective down-regulation of ENO1-A1 which we identified as a phosphoprotein. RA caused the dephosphorylation of ENO1-A1. Both, RA-mediated and specific knock-down of ENO1/MBP-1 resulted in reduction of c-Myc oncoprotein, and simultaneously decreased proliferation rates of FTC-133 and FTC-238 cell lines. In summary, the RA-mediated down-regulation of the ENO1 gene products and c-Myc oncoprotein provides a novel molecular mechanism facilitating the anti-proliferative effect of RA in human thyroid carcinoma cells and suggests new pathways for supportive RA therapies.