Tan Sipin, Tan Jin, Tan Sichuang, Zhao Shuai, Cao Xiaoxia, Chen Zhikang, Weng Qiaocheng, Zhang Huali, Wang Kangkai, Zhou Jiang, Xiao Xianzhong
Laboratory of Shock, Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410008, People's Republic of China.
Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Hunan 410011, People's Republic of China.
Oncotarget. 2016 Aug 16;7(33):53702-53711. doi: 10.18632/oncotarget.10724.
For the first time, dramatically decreased Dp71 protein and mRNA was found in 34 pairs of resected primary gastric adenocarcinoma. Immunohistochemistry identified Dp71 expression suppressed in 72.2% of 104 gastric cancer patients. The decreased Dp71 expression was significantly correlated with cancer differentiation (P=0.001) and lymph vascular invasion (p=0.041). Decreased Dp71 expression was associated with a poor gastric adenocarcinoma prognosis (P=0.001). Significantly less Dp71 mRNA and protein were found in BGC823, SGC7901, AGS compared with GES-1. Via increasing lamin B1 mRNA and protein, enforced Dp71d and Dp71f expression resulted in SGC7901 proliferation inhibition. Co-IP proved interaction of Dp71 with lamin B1 in GES-1 cells. Further expression characterization showed reduced lamin B1 in gastric cancer tissue and cancer cells. Increasing lamin B1 expression results in the growth inhibition of SGC7901, which suggests that Dp71-lamin B1 protein complex plays an important role for the newly identified tumor suppressive function of Dp71.
首次在34对切除的原发性胃腺癌中发现Dp71蛋白和mRNA显著减少。免疫组织化学鉴定出104例胃癌患者中有72.2%的Dp71表达受到抑制。Dp71表达降低与癌症分化(P = 0.001)和淋巴管侵犯(P = 0.041)显著相关。Dp71表达降低与胃腺癌预后不良相关(P = 0.001)。与GES-1相比,在BGC823、SGC7901、AGS中发现的Dp71 mRNA和蛋白明显较少。通过增加层粘连蛋白B1 mRNA和蛋白,强制表达Dp71d和Dp71f导致SGC7901增殖受到抑制。免疫共沉淀证明在GES-1细胞中Dp71与层粘连蛋白B1相互作用。进一步的表达特征显示胃癌组织和癌细胞中层粘连蛋白B1减少。增加层粘连蛋白B1表达导致SGC7901生长受到抑制,这表明Dp71-层粘连蛋白B1蛋白复合物对新发现的Dp71肿瘤抑制功能起重要作用。