Du Hailei, Che Jiamin, Shi Minmin, Zhu Lianggang, Hang Jun Biao, Chen Zhongyuan, Li Hecheng
Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
Institute of Digestive Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
Oncol Lett. 2017 Dec;14(6):6823-6828. doi: 10.3892/ol.2017.7015. Epub 2017 Sep 21.
Beclin 1 has a central role in the regulation of autophagy, differentiation, apoptosis resistance, tumorigenesis and cancer progression. The role of Beclin 1 in the development of esophageal squamous cell carcinoma (ESCC) and its subsequent progression is not fully characterized. In the present study, the role of Beclin 1 and autophagy in ESCC was evaluated. The expression of Beclin 1 mRNA and protein levels in human ESCC tumor and adjacent normal esophageal tissue was measured. Beclin 1 mRNA and protein were significantly lower in tumor tissue than in normal esophageal tissue (P<0.05). Cells of the less differentiated esophageal tumors expressed lower Beclin 1 mRNA and protein (P<0.05). Tumors from patients in early clinical stages (I/II) exhibited significantly higher Beclin 1 mRNA and protein expression levels than patients with tumors in mid-to-late stages (III/IV; P<0.05). Tumors from patients with lymph node metastasis exhibited significantly lower Beclin 1 mRNA and protein expression levels compared with tumors from patients without lymph node involvement (P<0.05). Beclin 1 downregulation was demonstrated to significantly upregulate invasion by ESCC EC9706 cells (P<0.01), and downregulate the number of acidic vesicular organelles, a process associated with autophagy. These results suggest that the expression of Beclin 1 is associated with the occurrence and development of ESCC. Measuring the Beclin 1 expression of tumors from patient may improve the understanding of the prognosis of patients with ESCC.
Beclin 1在自噬、分化、抗凋亡、肿瘤发生及癌症进展的调控中起核心作用。Beclin 1在食管鳞状细胞癌(ESCC)发生及后续进展中的作用尚未完全明确。在本研究中,对Beclin 1及自噬在ESCC中的作用进行了评估。检测了人ESCC肿瘤组织及相邻正常食管组织中Beclin 1 mRNA及蛋白水平。肿瘤组织中Beclin 1 mRNA及蛋白水平显著低于正常食管组织(P<0.05)。低分化食管肿瘤细胞中Beclin 1 mRNA及蛋白表达较低(P<0.05)。临床早期(I/II期)患者的肿瘤组织中Beclin 1 mRNA及蛋白表达水平显著高于中晚期(III/IV期)患者(P<0.05)。有淋巴结转移患者的肿瘤组织中Beclin 1 mRNA及蛋白表达水平显著低于无淋巴结转移患者的肿瘤组织(P<0.05)。研究表明,Beclin 1表达下调可显著上调ESCC EC9706细胞的侵袭能力(P<0.01),并下调与自噬相关的酸性囊泡细胞器数量。这些结果提示,Beclin 1表达与ESCC的发生发展相关。检测患者肿瘤组织中Beclin 1表达情况可能有助于提高对ESCC患者预后的认识。