HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (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.

¹ AG Experimentelle & Chirurgische Onkologie, Universitätsklinik und Poliklinik für Allgemein-, Viszeral- und Gefäßchirurgie, Martin-Luther Universität, Magdeburger Strasse 18, 06097 Halle/S., Germany² Universitätsklinik und Poliklinik für Kinderchirurgie, Martin-Luther Universität, Halle, Germany³ Institut für Physiologische Chemie, Martin-Luther Universität, Halle, Germany⁴ Institut für Experimentelle Endokrinologie, Charité, Universitätsmedizin Berlin, Berlin, Germany⁵ Orthopedic Center for Musculoskeletal Research, University of Wuerzburg, Wuerzburg, Germany⁶ Department of Human Anatomy & Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada

(Correspondence should be addressed to C Hoang-Vu; Email: hoang-vu{at}medizin.uni-halle.de)

Retinoic acid (RA) acts as an anti-proliferative and redifferentiation agent in the therapy of thyroid carcinoma. Our previous studies demonstrated that pretreatment 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 the 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 (2D) screening of the proteins related to ATP metabolism and western blot analysis revealed -enolase (ENO1) to be down-regulated in FTC-133 and FTC-238 cells after RA treatment. 2D gel detection and mass spectrometric analysis revealed that ENO1 existed as three separate protein spots of distinct pIs (ENO1–A1–A3). Comparative 2D difference gel electrophoresis analysis of fluorescently labeled protein samples of RA-treated and untreated FTC-133 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 the reduction of 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 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.