Li Xiuguo, Pan Xinliang, Zhang Hui, Lei Dapeng, Liu Dayu, Xu Fenglei, Luan Xinyong
Department of Otolaryngology, Qilu Hospital of Shandong University, 107 Wenhua xi Road, Jinan, Shandong 250012, People's Republic of China.
J Cancer Res Clin Oncol. 2008 May;134(5):609-15. doi: 10.1007/s00432-007-0325-7. Epub 2007 Oct 9.
The aim of this study was to determine the expression of cellular FLICE-like inhibitory protein (cFLIP) in head and neck squamous cell carcinoma (HNSCC) and revealed its possible correlation to Fas protein and tumour clinical parameters.
The expression of cFLIP was analysed in 58 HNSCC samples and 30 morphologically normal tissues adjacent to the carcinomas using immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. Furthermore, its possible correlation to the expression of Fas protein and tumour clinicopathologic parameters were discussed.
Cellular FLICE-like inhibitory protein was demonstrated to be up regulated in most HNSCC than in normal tissues by immunohistochemistry (p<0.01). Although the mRNA levels of both isoforms of cFLIP, long form (cFLIP(L)) and short form (cFLIP(S)), in HNSCC were higher than those in normal tissues (p<0.01), only cFLIP(L) protein could be detected by western blot. Furthermore, the expression of cFLIP(L) protein was significantly associated with tumour clinical stage (p<0.01) and lymph node metastasis (p=0.01). Since all of the tumours with Fas immunostaining also express cFLIP protein, there was no significant correlation between them (p>0.05).
Overexpression of cFLIP(L) is a frequent event in HNSCC and HNSCC cells in vivo may need it to evade apoptosis mediated by Fas or other receptors, which might contribute to tumour development and progression.
本研究旨在确定细胞FLICE样抑制蛋白(cFLIP)在头颈部鳞状细胞癌(HNSCC)中的表达,并揭示其与Fas蛋白及肿瘤临床参数之间的可能关联。
采用免疫组织化学、逆转录-聚合酶链反应(RT-PCR)及蛋白质印迹分析,对58例HNSCC样本及30例癌旁形态学正常组织中的cFLIP表达进行分析。此外,还探讨了其与Fas蛋白表达及肿瘤临床病理参数之间的可能关联。
免疫组织化学显示,大多数HNSCC中细胞FLICE样抑制蛋白的表达高于正常组织(p<0.01)。虽然HNSCC中cFLIP两种异构体(长型(cFLIP(L))和短型(cFLIP(S)))的mRNA水平均高于正常组织(p<0.01),但蛋白质印迹仅能检测到cFLIP(L)蛋白。此外,cFLIP(L)蛋白的表达与肿瘤临床分期(p<0.01)及淋巴结转移(p=0.01)显著相关。由于所有Fas免疫染色阳性的肿瘤也表达cFLIP蛋白,因此二者之间无显著相关性(p>0.05)。
cFLIP(L)的过表达在HNSCC中较为常见,体内HNSCC细胞可能需要它来逃避Fas或其他受体介导的凋亡,这可能有助于肿瘤的发生和发展。