Core Unit Chip Application, Institute of Human Genetics, 07740 Jena, Germany.
Mol Med Rep. 2011 Jan-Feb;4(1):157-61. doi: 10.3892/mmr.2010.393. Epub 2010 Nov 5.
We previously identified transthyretin (TTR) and its posttranslational modifications as a down-regulated marker in mycosis fungoides (MF), a benign subtype of cutaneous T-cell lymphoma (CTCL). In order to more precisely understand the biological role of TTR in the etiology of MF, it is essential to clarify the pathways of progression by identifying further interacting proteins. This study is the first to combine blue native polyacrylamide gel electrophoresis (BN-PAGE) with surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to detect new TTR interaction partners and to determine whether these TTR interaction partners can themselves be used as biomarkers. By this procedure, apolipoprotein A1, which was additionally found to be down-regulated in the serum of MF patients, apolipoprotein A4, retinol binding protein 4 (RBP-4), and retinoid X receptor β (RXR-β) were identified as interaction partners of TTR. The RXR family plays a role in cell differentiation and proliferation and is known to be the target of bexarotene, which is used in the treatment of CTCL. In conclusion, the combination of BN-PAGE and SELDI-TOF-MS used in this study allowed for the detection of protein interaction partners, which, in the case of RBP-4 and RXR, indicated a connection between the common tumor marker TTR and tumor progression in CTCL.
我们之前已经鉴定了转甲状腺素蛋白（TTR）及其翻译后修饰物是蕈样肉芽肿（MF）的下调标志物，MF 是皮肤 T 细胞淋巴瘤（CTCL）的良性亚型。为了更精确地理解 TTR 在 MF 发病机制中的生物学作用，通过鉴定进一步的相互作用蛋白阐明进展途径是至关重要的。本研究首次将蓝色非变性聚丙烯酰胺凝胶电泳（BN-PAGE）与表面增强激光解吸/电离飞行时间质谱（SELDI-TOF-MS）相结合，以检测新的 TTR 相互作用伙伴，并确定这些 TTR 相互作用伙伴本身是否可用作生物标志物。通过该程序，发现载脂蛋白 A1（apoA1）在 MF 患者的血清中也下调，载脂蛋白 A4、视黄醇结合蛋白 4（RBP-4）和维甲酸 X 受体 β（RXR-β）被鉴定为 TTR 的相互作用伙伴。RXR 家族在细胞分化和增殖中起作用，并且已知是贝沙罗汀的靶标，贝沙罗汀用于 CTCL 的治疗。总之，本研究中使用的 BN-PAGE 和 SELDI-TOF-MS 的组合允许检测蛋白相互作用伙伴，在 RBP-4 和 RXR 的情况下，表明常见的肿瘤标志物 TTR 与 CTCL 中的肿瘤进展之间存在联系。
