Husvik Camilla, Bryne Magne, Halstensen Trond S
Department of Oral Biology, University of Oslo, Oslo, Norway.
Eur J Oral Sci. 2009 Dec;117(6):663-8. doi: 10.1111/j.1600-0722.2009.00682.x.
Epidermal growth factor (EGF)-induced cyclooxygenase-2 (COX-2) expression in squamous cell carcinomas is mediated through the extracellular signal-regulated kinase 1/2 and p38 pathways. Examination of a basaloid and a conventional oral squamous cell carcinoma cell line revealed that inhibition of c-Jun N-terminal kinase (JNK) with SP600125 increased EGF-induced (but not basal) COX-2 transcription 1.5-1.9-fold in extracellular signal-regulated kinase 1/2 and p38 pathway-dependent manners. Although JNK may phosphorylate the cyclosporine A-sensitive transcription factor, nuclear factor of activated T cells c3, it was seemingly not involved because cyclosporine A did not reduce EGF-induced COX-2 expression. Thus, JNK negatively regulated EGF-induced extracellular signal-regulated kinase 1/2 and/or p38-mediated COX-2 transcription, presumably through activating an unidentified phosphatase.
表皮生长因子（EGF）诱导的环氧化酶-2（COX-2）在鳞状细胞癌中的表达是通过细胞外信号调节激酶1/2和p38途径介导的。对一种基底样和一种传统口腔鳞状细胞癌细胞系的研究表明，用SP600125抑制c-Jun氨基末端激酶（JNK）以细胞外信号调节激酶1/2和p38途径依赖的方式使EGF诱导的（而非基础的）COX-2转录增加1.5至1.9倍。尽管JNK可能使环孢素A敏感的转录因子活化T细胞核因子c3磷酸化，但似乎并非如此，因为环孢素A并未降低EGF诱导的COX-2表达。因此，JNK负向调节EGF诱导的细胞外信号调节激酶1/2和/或p38介导的COX-2转录，可能是通过激活一种未知的磷酸酶来实现的。
