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螺旋-环-螺旋蛋白Id2在人类胰腺癌中过度表达。

The helix-loop-helix protein Id2 is overexpressed in human pancreatic cancer.

作者信息

Kleeff J, Ishiwata T, Friess H, Büchler M W, Israel M A, Korc M

机构信息

Department of Medicine, University of California, Irvine 92697, USA.

出版信息

Cancer Res. 1998 Sep 1;58(17):3769-72.

PMID:9731481
Abstract

Id2 belongs to the Id family of helix-loop-helix (HLH) proteins, which upon heterodimerization with basic HLH proteins prevent basic HLH proteins from DNA binding. Proteins of the Id family act as negative regulatory transcriptional factors, and their expression correlates with cell proliferation and arrested differentiation in many cell lineages. In this study, we characterized the expression of Id2 in normal and cancerous pancreatic tissues. Pancreatic cancers markedly overexpressed Id2 mRNA in comparison to the normal pancreas. Furthermore, there was abundant Id2 immunoreactivity in the cancer cells within the pancreatic tumor mass. In PANC-1 human pancreatic cancer cells, steady-state Id2 mRNA levels increased upon serum addition and decreased after induction of differentiation with either sodium butyrate or 12-O-tetradecanoylphorbol-13-acetate. Inhibition of Id2 expression with Id2 antisense oligonucleotides inhibited the growth of these cells, whereas random and sense oligonucleotides were without effect. These findings suggest that Id2 may have a role in human pancreatic cancer.

摘要

Id2属于螺旋-环-螺旋(HLH)蛋白的Id家族,该家族蛋白与碱性HLH蛋白异源二聚化后,会阻止碱性HLH蛋白与DNA结合。Id家族蛋白作为负性调节转录因子,其表达与许多细胞谱系中的细胞增殖和分化停滞相关。在本研究中,我们对Id2在正常胰腺组织和癌组织中的表达进行了表征。与正常胰腺相比,胰腺癌中Id2 mRNA明显过表达。此外,胰腺肿瘤块内的癌细胞中有丰富的Id2免疫反应性。在PANC-1人胰腺癌细胞中,添加血清后Id2的稳态mRNA水平升高,用丁酸钠或12-O-十四烷酰佛波醇-13-乙酸酯诱导分化后则降低。用Id2反义寡核苷酸抑制Id2表达可抑制这些细胞的生长,而随机寡核苷酸和正义寡核苷酸则无此作用。这些发现表明,Id2可能在人类胰腺癌中发挥作用。

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