Wang Chuan, Chen Qiang, Hamajima Yuki, Sun Wei, Zheng Yi-Qing, Hu Xiao-Hua, Ondrey Frank G, Lin Ji-Zhen
The Cancer Center and Fujian Key Laboratory of Translational Cancer Medicine, Union Hospital, Fujian Medical University, Fuzhou, Fujian 350001, PR China.
Chin J Cancer. 2012 Sep;31(9):430-9. doi: 10.5732/cjc.011.10454. Epub 2012 Jul 26.
Squamous cell carcinoma(SCC) is a significant cause of cancer morbidity and mortality worldwide, with an incidence of up to 166 cases per 100 000 population. It arises in the skin, upper aerodigestive tract, lung, and cervix and affects more than 200 000 Americans each year. We report here that a microarray experiment comparing 41 SCC and 13 normal tissue specimens showed that Id2, a gene that controls the cell cycle, was significantly up-regulated in SCC. Enforced expression of Id2 in vitro stimulated the proliferation of SCC cells and up-regulated the transcription of nuclear factor kappa B (NF-κB) and cyclin D1. Enhancement of the NF-κB activity with p65 significantly increased the cell proliferation and the transcription of cyclin D1, whereas inhibition of the NF-κB activity with I kappa B alpha mutant (IκBαM) and pyrroline dithiocarbamate (PDTC) abrogated cell proliferation and transcription of cyclin D1. Furthermore, a mutated NF-κB binding site in the cyclin D1 promoter fully abrogated the Id2-induced transcription of cyclin D1. Taken together, these data indicate that Id2 induces SCC tumor growth and proliferation through the NF-κB/cyclin D1 pathway.
鳞状细胞癌（SCC）是全球癌症发病和死亡的一个重要原因，发病率高达每10万人166例。它发生于皮肤、上消化道、肺和子宫颈，每年影响超过20万美国人。我们在此报告，一项比较41个SCC组织标本和13个正常组织标本的微阵列实验表明，Id2（一种控制细胞周期的基因）在SCC中显著上调。在体外强制表达Id2可刺激SCC细胞增殖，并上调核因子κB（NF-κB）和细胞周期蛋白D1的转录。用p65增强NF-κB活性可显著增加细胞增殖和细胞周期蛋白D1的转录，而用IκBα突变体（IκBαM）和吡咯烷二硫代氨基甲酸盐（PDTC）抑制NF-κB活性则可消除细胞增殖和细胞周期蛋白D1的转录。此外，细胞周期蛋白D1启动子中的一个突变NF-κB结合位点完全消除了Id2诱导的细胞周期蛋白D1转录。综上所述，这些数据表明Id2通过NF-κB/细胞周期蛋白D1途径诱导SCC肿瘤生长和增殖。
