Universitätsklinik und Poliklinik für Allgemein-, Viszeral- und Gefässchirurgie, Martin-Luther Universität, 06097 Halle, Germany.
Mol Cell Endocrinol. 2010 Aug 30;325(1-2):110-7. doi: 10.1016/j.mce.2010.05.022. Epub 2010 Jun 9.
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.
我们之前的研究表明，视黄酸（RA）诱导的关键糖酵解酶 ENO1 和促进增殖的 c-Myc 的减少，导致滤泡性甲状腺癌细胞系 FTC-133 和 FTC-238 的活力和侵袭性降低。通过二维电泳和质谱分析，我们鉴定了受 RA 处理影响的蛋白质。除了先前报道的 ENO1 表达减少外，我们还发现 RA 导致甘油醛-3-磷酸脱氢酶（GAPDH）、丙酮酸激酶同工酶 M1/M2（PKM1/M2）、肽基脯氨酰顺反异构酶 A（PPIA）、转酮醇酶（TKT）、膜联蛋白 A2（ANXA2）、谷胱甘肽 S-转移酶 P（GSTP1）和过氧化物还原酶 2（PRDX2）的水平显著降低，与未处理的对照组相比。与甲状腺肿和腺瘤组织相比，在甲状腺组织中研究的相同蛋白质在滤泡性、乳头状和未分化甲状腺癌中明显上调。这些发现为 RA 介导的抗肿瘤和再分化治疗确定了新的靶蛋白，并为甲状腺癌的治疗提供了新的见解。
