Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells
Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells
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DOI：
10.1038/sj.onc.1210951
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发表时间：
2008-05-01
期刊：
影响因子：
8
通讯作者：
Miyazaki, M.
中科院分区：
文献类型：
--
作者：
Takano, S.;Yoshitomi, H.;Miyazaki, M.
胰腺癌仍然是最致命的疾病之一，需要建立新的治疗方法。本研究的目的是通过蛋白质组学的方法寻找与胰腺癌进展相关的新因素。我们比较了手术前后血清蛋白PRO的变化。Ling取自胰腺癌根治性切除患者，采用表面增强激光解吸电离飞行时间质谱仪。6630Da和6420Da峰值强度水平术前显著高于术后(P<；0.002)。氨基酸序列分析表明这些蛋白质为载脂蛋白C-1(ApoC-1)。术前血清ApoC-1水平升高与预后不良密切相关。此外，ApoC-1在胰腺癌上皮细胞中大量表达，并在体外培养的胰腺癌细胞株的培养液中检测到ApoC-1，提示癌细胞分泌ApoC-1。短干扰RNA抑制ApoC-1的表达可抑制细胞增殖，诱导胰腺癌细胞凋亡。ApoC-1在胰腺癌细胞中的特异性表达及其在阻止自发性细胞凋亡中的作用表明，ApoC-1参与了胰腺癌的侵袭性，有望成为新的治疗靶点。
Pancreatic cancer still remains one of the most lethal diseases and establishment of new therapy is needed. The purpose of this study is to find novel factors involved in pancreatic cancer progression by proteomic approach. We compared pre- and postoperative serum protein pro. ling obtained from pancreatic cancer patients who had curative pancreatectomy using surface-enhanced laser desorption ionization time-of-flight mass spectrometry. The peak intensity levels of both 6630 and 6420 Da were significantly higher in the preoperative serum than in the postoperative serum (P < 0.002). Sequential amino acid analysis identified these proteins to be apolipoprotein C-1 (ApoC-1). The high level of ApoC-1 in preoperative serum significantly correlated with poor prognosis. Furthermore, ApoC-1 was abundantly expressed in pancreas neoplastic epithelium, and was detected in the culture medium of the pancreatic cancer cell line in vitro, which suggests that cancer cells secrete ApoC-1. Inhibition of ApoC-1 expression by short interfering RNA suppressed cell proliferation and induced apoptosis of pancreatic cancer cells. The specific expression of ApoC-1 and its role in preventing from spontaneous apoptosis in pancreatic cancer cells suggest that ApoC-1 contributes to the aggressiveness of pancreatic cancer and will be useful as a new therapeutic target.