Chiriva-Internati Maurizio, Ferrari Raffaele, Prabhakar Madhavi, Yu Yuefei, Baggoni Luigi, Moreno Jorge, Gagliano Nicoletta, Portinaro Nicola, Jenkins Marjorie R, Frezza Eldo E, Hardwicke Fred, D'Cunha Nicholas, Kast Wmartin, Cobos Everardo
Department of Microbiology and Immunology, Texas Tech University Health Sciences Center and Southwest Cancer Treatment and Research Center, Lubbock, TX, USA.
J Transl Med. 2008 Apr 2;6:15. doi: 10.1186/1479-5876-6-15.
Multiple Myeloma is a cancer of B plasma cells, which produce non-specific antibodies and proliferate uncontrolled. Due to the potential relapse and non-specificity of current treatments, immunotherapy promises to be more specific and may induce long-term immunity in patients. The pituitary tumor transforming gene 1 (PTTG-1) has been shown to be a novel oncogene, expressed in the testis, thymus, colon, lung and placenta (undetectable in most other tissues). Furthermore, it is over expressed in many tumors such as the pituitary adenoma, breast, gastrointestinal cancers, leukemia, lymphoma, and lung cancer and it seems to be associated with tumorigenesis, angiogenesis and cancer progression. The purpose was to investigate the presence/rate of expression of PTTG-1 in multiple myeloma patients.
We analyzed the PTTG-1 expression at the transcriptional and the protein level, by PCR, immunocytochemical methods, Dot-blot and ELISA performed on patient's sera in 19 multiple myeloma patients, 6 different multiple myeloma cell lines and in normal human tissue.
We did not find PTTG-1 presence in the normal human tissue panel, but PTTG-1 mRNA was detectable in 12 of the 19 patients, giving evidence of a 63% rate of expression (data confirmed by ELISA). Four of the 6 investigated cell lines (66.6%) were positive for PTTG-1. Investigations of protein expression gave evidence of 26.3% cytoplasmic expression and 16% surface expression in the plasma cells of multiple myeloma patients. Protein presence was also confirmed by Dot-blot in both cell lines and patients.
We established PTTG-1's presence at both the transcriptional and protein levels. These data suggest that PTTG-1 is aberrantly expressed in multiple myeloma plasma cells, is highly immunogenic and is a suitable target for immunotherapy of multiple myeloma.
多发性骨髓瘤是一种B浆细胞癌症，B浆细胞产生非特异性抗体并不受控制地增殖。由于当前治疗存在潜在复发风险且缺乏特异性，免疫疗法有望更具特异性，并可能在患者中诱导长期免疫。垂体肿瘤转化基因1（PTTG - 1）已被证明是一种新型癌基因，在睾丸、胸腺、结肠、肺和胎盘中表达（在大多数其他组织中未检测到）。此外，它在许多肿瘤中过度表达，如垂体腺瘤、乳腺癌、胃肠道癌、白血病、淋巴瘤和肺癌，并且似乎与肿瘤发生、血管生成和癌症进展有关。目的是研究PTTG - 1在多发性骨髓瘤患者中的存在情况/表达率。
我们通过聚合酶链反应（PCR）、免疫细胞化学方法、斑点印迹法和酶联免疫吸附测定（ELISA），对19例多发性骨髓瘤患者、6种不同的多发性骨髓瘤细胞系以及正常人体组织进行检测，分析PTTG - 1在转录水平和蛋白质水平的表达情况。
在正常人体组织样本中未发现PTTG - 1的存在，但在19例患者中的12例检测到PTTG - 1 mRNA，表达率为63%（ELISA数据证实）。6种研究的细胞系中有4种（66.6%）PTTG - 1呈阳性。对蛋白质表达的研究表明，多发性骨髓瘤患者浆细胞中26.3%存在细胞质表达，16%存在表面表达。通过斑点印迹法在细胞系和患者中均证实了蛋白质的存在。
我们确定了PTTG - 1在转录水平和蛋白质水平均存在。这些数据表明，PTTG - 1在多发性骨髓瘤浆细胞中异常表达，具有高度免疫原性，是多发性骨髓瘤免疫治疗的合适靶点。
