雄激素受体信号途径促进男性食管鳞癌细胞生长机制研究  

Androgen receptor signaling pathway promotes the proliferation of male esophageal squamous cancer cells

作　　者：沙海洋[1] 李文清 徐明怡[1] 史春霞[1] 耿晓[1] SHA Hai-yang;LI Wen-qing;XUMing-yi;SHI Chun-xia;GENG Xiao(Otolaryngological Department,Shandong Academy of Occupational Health and Occupational Medicine,Jinan 250062,P.R.China;Cancer Prevention Center,Second Hospital of Shandong University,Jinan 250033 R.China)

机构地区：[1]山东省职业卫生与职业病防治研究院耳鼻喉科,山东济南250062 [2]山东大学第二医院肿瘤防治中心,山东济南250033

出　　处：《中华肿瘤防治杂志》2019年第24期1872-1875,1894,共5页Chinese Journal of Cancer Prevention and Treatment

摘　　要：目的食管癌是人类常见的恶性肿瘤,男性患者发病率明显高于女性,男性激素水平在该病的发生发展中的作用目前尚不明确。本研究探讨雄激素受体(androgen receptor,AR)信号传导途径在男性食管鳞癌细胞生长中的作用机制。方法蛋白质印迹法分别检测2016-02-01-2018-02-01山东大学第二医院经手术切除的男性食管鳞癌肿瘤组织、瘤周正常食管组织及OE21、RJEC-2、EC109和EC9706等食管鳞癌细胞系中AR的表达;并选用OE21细胞系进一步研究,经转化生长因子-β1(transforming growth factor-β1,TGF-β1)及5α二氢睾酮(5α-dihydrotestosterone,DHT)单独及联合干预后,四甲基偶氮唑盐(methyl thiazolyl tetrazolium,MTT)实验和凋亡实验分别检测OE21细胞增殖及凋亡,免疫沉淀和免疫印迹法分别检测AR和SMAD3(TGF-β1途径主要信号因子)蛋白及其蛋白磷酸化水平。结果相较于周围正常食管组织,AR在食管鳞癌肿瘤组织有更高表达,且4种细胞系中均发现AR表达;10ng/mL TGF-β1可抑制OE21细胞生长约50%(P<0.05),但DHT可消弱TGF-β1对OE21细胞的抑制作用;DHT并不能影响SMAD3蛋白及其磷酸化水平,同样,TGF-β1也不能影响AR蛋白及其磷酸化水平。磷酸化水平的AR通过与磷酸化水平的SMAD3结合,进而发挥对食管鳞癌细胞生长的调节作用。结论AR信号传导通路可能通过抑制TGF-β1受体信号进而促进男性食管鳞癌细胞的生长。OBJECTIVE Esophageal cancer is a common malignant tumor in human beings.The incidence of male patients is significantly higher than that of female patients.The role of male hormone level in the occurrence and development of this disease is still unclear.This study explores the role of AR signaling pathway in esophageal squamous cancer(ESC).METHODS The expression of AR in male patients with ESC tumor tissue and periphery normal esophageal tissues and 4 human esophageal cancer cell lines was detected by Western blot.OE21 ESC line was selected for the further study.MTT experiment and apoptosis assay were used to detect the proliferation and apoptosis of OE21 cells respectively by the intervention of TGF-β1/DHT.Total protein and the phosphorylated protein of AR and SMAD3(the main signal factor of TGF-β1 pathway)were detected by Immunoprecipitation and immunoblotting.RESULTS Higher AR expression was detected in ESC,compared to the periphery normal esophageal tissue(NET)in patients.TGF-β1 can inhibit the growth of OE21 cells by about 50%with P<0.05,but the inhibitory effect can be abolished by DHT.DHT cannot affect SMAD3 protein and its phosphorylation level,and likewise,TGF-β1 cannot affect AR protein and its phosphorylation level.pAR combines with pSMAD3 to play a regulating effect on the growth of ESC cells.CONCLUSION Taken together,our study suggests that AR signaling pathway may promote tumorigenesis of ESC in adult men by inhibiting TGF-β1 receptor signaling.

关 键 词：雄激素受体 5α二氢睾酮 食管鳞癌 转化生长因子-Β1 SMAD3 

分 类 号：R736.1[医药卫生—肿瘤]