Wagener N, Crnković-Mertens I, Vetter C, Macher-Göppinger S, Bedke J, Gröne E F, Zentgraf H, Pritsch M, Hoppe-Seyler K, Buse S, Haferkamp A, Autschbach F, Hohenfellner M, Hoppe-Seyler F
German Cancer Research Center, Molecular Therapy of Virus-Associated Cancers (F065), Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.
Br J Cancer. 2007 Nov 5;97(9):1271-6. doi: 10.1038/sj.bjc.6604028. Epub 2007 Oct 30.
The antiapoptotic Livin/ML-IAP gene has recently gained much attention as a potential new target for cancer therapy. Reports indicating that livin is expressed almost exclusively in tumours, but not in the corresponding normal tissue, suggested that the targeted inhibition of livin may present a novel tumour-specific therapeutic strategy. Here, we compared the expression of livin in renal cell carcinoma and in non-tumorous adult kidney tissue by quantitative real-time reverse transcription-PCR, immunoblotting, and immunohistochemistry. We found that livin expression was significantly increased in tumours (P=0.0077), but was also clearly detectable in non-tumorous adult kidney. Transcripts encoding Livin isoforms alpha and beta were found in both renal cell carcinoma and normal tissue, without obvious qualitative differences. Livin protein in renal cell carcinoma samples exhibited cytoplasmic and/or nuclear staining. In non-tumorous kidney tissue, Livin protein expression was only detectable in specific cell types and restricted to the cytoplasm. Thus, whereas the relative overexpression of livin in renal cell carcinoma indicates that it may still represent a therapeutic target to increase the apoptotic sensitivity of kidney cancer cells, this strategy is likely to be not tumour-specific.
抗凋亡蛋白Livin/ML-IAP基因作为一种潜在的癌症治疗新靶点,近来备受关注。有报道指出,Livin几乎仅在肿瘤组织中表达,而在相应的正常组织中不表达,这提示对Livin进行靶向抑制可能是一种新的肿瘤特异性治疗策略。在此,我们通过定量实时逆转录PCR、免疫印迹和免疫组化,比较了Livin在肾细胞癌和非肿瘤性成人肾组织中的表达情况。我们发现,Livin在肿瘤组织中的表达显著增加(P=0.0077),但在非肿瘤性成人肾组织中也可明显检测到。在肾细胞癌和正常组织中均发现了编码Livinα和β亚型的转录本,且无明显的定性差异。肾细胞癌样本中的Livin蛋白呈细胞质和/或细胞核染色。在非肿瘤性肾组织中,Livin蛋白表达仅在特定细胞类型中可检测到,且局限于细胞质。因此,尽管Livin在肾细胞癌中的相对过表达表明它可能仍是提高肾癌细胞凋亡敏感性的治疗靶点,但该策略可能并非肿瘤特异性的。