Gattenlöhner Stefan, Stühmer Thorsten, Leich Ellen, Reinhard Matthias, Etschmann Benjamin, Völker Hans-Ulrich, Rosenwald Andreas, Serfling Edgar, Bargou Ralf Christian, Ertl Georg, Einsele Hermann, Müller-Hermelink Hans-Konrad
Institute of Pathology, University of Würzburg, Josef-Schneiderstr.2, D-97080 Würzburg, Germany.
Am J Pathol. 2009 Apr;174(4):1160-71. doi: 10.2353/ajpath.2009.080647. Epub 2009 Feb 26.
Alternative splicing of transcripts from many cancer-associated genes is believed to play a major role in carcinogenesis as well as in tumor progression. Alternative splicing of one such gene, the neural cell adhesion molecule CD56 (NCAM), impacts the progression, inadequate therapeutic response, and reduced total survival of patients who suffer from numerous malignant neoplasms. Although previous investigations have determined that CD56 exists in three major isoforms (CD56(120kD), CD56(140kD), and CD56(180kD)) with individual structural and functional properties, neither the expression profiles nor the functional relevance of these isoforms in malignant tumors have been consistently investigated. Using new quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) strategies and novel CD56 isoform-specific antibodies, CD56(140kD) was shown to be exclusively expressed in a number of highly malignant CD56(+) neoplasms and was associated with the progression of CD56(+) precursor lesions of unclear malignant potential. Moreover, only CD56(140kD) induced antiapoptotic/proliferative pathways and specifically phosphorylated calcium-dependent kinases that are relevant for tumorigenesis. We conclude, therefore, that the specific detection of CD56 isoforms will help to elucidate their individual functions in the pathogenesis and progression of malignant neoplasms and may have a positive impact on the development of CD56-based immunotherapeutic strategies.
许多癌症相关基因转录本的可变剪接被认为在致癌过程以及肿瘤进展中起主要作用。其中一个基因，神经细胞黏附分子CD56（NCAM）的可变剪接，会影响众多恶性肿瘤患者的病情进展、治疗反应不佳以及总生存期缩短。尽管先前的研究已确定CD56存在三种主要异构体（CD56(120kD)、CD56(140kD)和CD56(180kD)），且各有独特的结构和功能特性，但这些异构体在恶性肿瘤中的表达谱及功能相关性尚未得到一致研究。利用新的定量逆转录聚合酶链反应（qRT-PCR）策略和新型CD56异构体特异性抗体，研究发现CD56(140kD)仅在一些高度恶性的CD56(+)肿瘤中表达，并与恶性潜能不明的CD56(+)前驱病变的进展相关。此外，只有CD56(140kD)诱导了与肿瘤发生相关的抗凋亡/增殖途径，并特异性磷酸化了钙依赖性激酶。因此，我们得出结论，对CD56异构体的特异性检测将有助于阐明它们在恶性肿瘤发病机制和进展中的各自功能，并可能对基于CD56的免疫治疗策略的开发产生积极影响。
