Fatty acid synthase is required for the proliferation of human oral squamous carcinoma cells
Fatty acid synthase is required for the proliferation of human oral squamous carcinoma cells
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DOI：
10.1016/j.oraloncology.2004.01.011
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发表时间：
2004-08-01
期刊：
影响因子：
4.8
通讯作者：
Graner, E
中科院分区：
文献类型：
--
作者：
Agostini, M;Silva, SD;Graner, E
脂肪酸合成酶（FAS）是负责从前体乙酰辅酶A和丙二酰辅酶A内源性合成饱和长链脂肪酸的酶。越来越多的证据表明FAS在几种人类癌症中过表达，如前列腺癌、乳腺癌、膀胱癌、肝癌、肺癌、黑色素瘤和口腔鳞状细胞癌（SCC）。本研究以人口腔鳞癌细胞系SCC-4、SCC-9、SCC-15和SCC-25为模型，探讨FAS在口腔癌发病机制中的作用。RT-PCR和蛋白质印迹实验表明，FAS的差异表达的四个口腔鳞状细胞癌细胞系，与SCC-9的最高产量其次是SCC-25。FAS在SCC-4和SCC-15中的表达也明显低于其他细胞系。增殖曲线和PCNA、Ki-67免疫细胞化学显示SCC-25具有最高的增殖潜能。此外，FAS活性特异性抑制剂浅蓝菌素能够显著降低口腔鳞癌细胞的增殖。雄激素受体在SCC-4、SCC-9和SCC-15中表达较低，而在SCC-25中未检测到，而EGFR和c-erb-B2在4种细胞系中均高表达。免疫细胞化学反应显示，SCC-25表达更高水平的EGF相比，其他三个细胞系。最后，口腔鳞状细胞癌细胞暴露于纳摩尔浓度的外源性EGF提出了减少FAS蛋白水平伴随着其增殖率下降。综上所述，我们的研究结果表明，FAS在口腔鳞癌细胞中以明显的雄激素非依赖性方式表达，并且其增殖是必需的。(C)2004爱思唯尔有限公司保留所有权利。
Fatty acid synthase (FAS) is the enzyme responsible for the endogenous synthesis of saturated tong-chain fatty acids from the precursors acetyl-CoA and malonyl-CoA. A growing body of evidence indicates that FAS is over expressed in several human cancers, such as prostate, breast, bladder, liver, lung, melanoma and oral squamous cell carcinoma (SCC). In the present study we used human oral SCC cell Lines (SCC-4, -9, -15 and -25) as a model to investigate the role of FAS in the pathogenesis of oral cancer. RT-PCR and western blot experiments demonstrated that FAS is differentially expressed by the four oral SCC cell lines, with the highest production in SCC-9 followed by SCC-25. FAS expression in SCC-4 and -15 was similarly tower than the other cell lines. Proliferation curves and immunocytochemistry for PCNA and Ki-67 demonstrated that SCC-25 has the highest proliferative potential. In addition, the specific inhibitor of FAS activity cerulenin was able to significantly reduce the proliferation of oral SCC cells. Expression of androgen receptor was tow in SCC-4, -9 and -15 and undetectable in SCC-25, whereas EGFR and c-erb-B2 were expressed in high amounts by the four cell lines. Immunocytochemical reactions showed that SCC-25 expresses higher levels of EGF compared to the other three cell lines. Finally, oral SCC cells exposed to nanomolar concentrations of exogenous EGF presented a reduction in the FAS protein levels concomitant with a decrease in their proliferation rates. Taken together, our results indicate that FAS is expressed in an apparently androgen-independent fashion in oral SCC cells and it is necessary for their proliferation. (C) 2004 Elsevier Ltd. All rights reserved.