Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China.
Mol Biol Rep. 2011 Nov;38(8):4903-11. doi: 10.1007/s11033-010-0632-y. Epub 2010 Dec 16.
The neuronal pentraxin II gene (NPTX2) is expressed in numerous tissues, such as the pancreas and the liver. While its activity in the brain is known to be regulated by neuronal activity, its function in the pancreas is unclear. In this study, we investigated the impact of NPTX2 on the proliferation, migration, invasion, apoptosis, and cell cycle of the pancreatic cancer cells. The expression levels of NPTX2 and their relation to the methylation level of the NPTX2 gene promoter in five pancreatic cancer cell lines were observed. The lower expression of NPTX2 in the cells was restored after the treatment of DNA methyltransferase inhibitor (5-aza-2'-deoxycytidine). Additionally, a full-length NPTX2 cDNA was transfected into pancreatic cancer cells (PANC-1) and we obtained the stably transfected cells (PANC-1-NPTX2). The ectopic NPTX2 expression significantly promoted G0-G1 arrest and cell apoptosis, and reduced cell proliferation, migration and invasion. Notably, the pro-apoptotic gene bax expression was significantly up-regulated while pro-survival gene bcl-2 did not significantly change in the stably transfected cells. Meanwhile, Cyclin D1 was significantly down-regulated. This study suggests that NPTX2, as a tumor-suppressor, plays an anti-tumor effect on pancreatic cancer and its low expression, due to promoter hypermethylation, may play a role in the tumorigenesis of pancreatic cancer.
神经元五联素 II 基因(NPTX2)在许多组织中表达,如胰腺和肝脏。虽然其在大脑中的活性已知受神经元活动调节,但在胰腺中的功能尚不清楚。在这项研究中,我们研究了 NPTX2 对胰腺癌细胞增殖、迁移、侵袭、凋亡和细胞周期的影响。观察了 NPTX2 在五种胰腺癌细胞系中的表达水平及其与 NPTX2 基因启动子甲基化水平的关系。用 DNA 甲基转移酶抑制剂(5-氮杂-2'-脱氧胞苷)处理后,细胞中 NPTX2 的低表达得到恢复。此外,将全长 NPTX2 cDNA 转染到胰腺癌细胞(PANC-1)中,获得稳定转染的细胞(PANC-1-NPTX2)。异位 NPTX2 表达显著促进 G0-G1 期阻滞和细胞凋亡,并减少细胞增殖、迁移和侵袭。值得注意的是,促凋亡基因 bax 的表达显著上调,而促生存基因 bcl-2 没有明显变化。同时,Cyclin D1 显著下调。这项研究表明,NPTX2 作为一种肿瘤抑制因子,对胰腺癌具有抗肿瘤作用,其启动子高甲基化导致的低表达可能在胰腺癌的发生中起作用。