Proteomic approach reveals novel targets for retinoic acid-mediated therapy of thyroid carcinoma.
Our previous studies demonstrated that retinoic acid (RA)-induced reduction of both, the key glycolytic enzyme ENO1 and proliferation-promoting c-Myc, resulted in decreased vitality and invasiveness of the follicular thyroid carcinoma cell lines FTC-133 and FTC-238. By employing two-dimensional electrophoresis and mass spectrometry, we identified proteins affected by RA treatment. In addition to previously reported decrease in ENO1 expression, we found that RA led to significantly reduced levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase isoenzymes M1/M2 (PKM1/M2), peptidyl-prolyl cis-trans isomerase A (PPIA), transketolase (TKT), annexin A2 (ANXA2), glutathione S-transferase P (GSTP1) and peroxiredoxin 2 (PRDX2) as compared to untreated control. The same proteins investigated on thyroid tissues were found to be significantly up-regulated in follicular, papillary and undifferentiated thyroid carcinomas when compared with goiter and adenoma tissues. These findings identify new target proteins for RA-mediated anti-tumor and re-differentiation therapies and provide novel insights into treatments for thyroid carcinoma.
Universitätsklinik und Poliklinik für Allgemein-, Viszeral- und Gefässchirurgie, Martin-Luther Universität, 06097 Halle, Germany.
Bogusz
B
Trojanowicz
Carsten
C
Sekulla
Kerstin
K
Lorenz
Josef
J
Köhrle
Rainer
R
Finke
Henning
H
Dralle
Cuong
C
Hoang-Vu
D000293:Adolescent; D000328:Adult; D000368:Aged; D054316:Biomarkers, Pharmacological / Q000032:analysis / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism*; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D040901:Proteomics; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014212:Tretinoin / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D014212:Tretinoin