Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Cancer Sci. 2011 Jun;102(6):1137-43. doi: 10.1111/j.1349-7006.2011.01936.x. Epub 2011 Apr 27.
A hypoxic microenvironment is a characteristic feature of pancreatic cancer, and induces the expressions of various genes involved in malignant behaviors. Insulin-induced gene 2 (Insig2) has recently been shown to be correlated with cellular invasion in colon cancer. However, there have been no reports regarding its expression in pancreatic cancer. In this study, we evaluated Insig2 mRNA expression and the biological function of Insig2 in pancreatic cancer. We measured Insig2 mRNA expression in cultured pancreatic cancer cell lines and invasive ductal carcinoma (IDC) cells, normal pancreatic epithelial cells, and pancreatic intraepithelial neoplasia cells obtained by laser-capture microdissection. We also investigated the effects of Insig2-targeting siRNAs on the cell proliferation and cell invasion of pancreatic cancer cell lines. All pancreatic cancer cell lines expressed Insig2 mRNA. The PANC-1 and MIA PaCa-2 pancreatic cancer cell lines showed >2-fold higher Insig2 mRNA expression levels under hypoxic conditions (1% O2) than under normoxic conditions (21% O2 ). Cell proliferation was significantly decreased in SUIT-2 cells and cell invasion was significantly decreased in SUIT-2, Capan-2, and CFPAC-1 cells after transfection of the Insig2-targeting siRNAs. In analyses of microdissected cells, cells from IDC tissues expressed significantly higher levels of Insig2 mRNA than normal pancreatic cells (P < 0.001) and pancreatic intraepithelial neoplasia cells (P = 0.082). In analyses of IDC cells, the levels of Insig2 mRNA expression were significantly higher in late-stage patients than in early-stage patients. The present data suggest that Insig2 is associated with the malignant potential of pancreatic cancer under hypoxic conditions.
缺氧微环境是胰腺癌的一个特征，诱导参与恶性行为的各种基因的表达。胰岛素诱导基因 2（Insig2）最近被证明与结肠癌的细胞侵袭有关。然而，目前还没有关于其在胰腺癌中的表达的报道。在本研究中，我们评估了 Insig2 mRNA 的表达及其在胰腺癌中的生物学功能。我们测量了培养的胰腺癌细胞系和浸润性导管癌（IDC）细胞、正常胰腺上皮细胞和激光捕获显微切割获得的胰腺上皮内瘤变细胞中 Insig2 mRNA 的表达。我们还研究了 Insig2 靶向 siRNA 对胰腺癌细胞系细胞增殖和细胞侵袭的影响。所有胰腺癌细胞系均表达 Insig2 mRNA。在缺氧条件（1% O2）下，PANC-1 和 MIA PaCa-2 胰腺癌细胞系的 Insig2 mRNA 表达水平高于常氧条件（21% O2），表达水平增加了 2 倍以上。在 SUIT-2 细胞中转染 Insig2 靶向 siRNA 后，细胞增殖显著减少，在 SUIT-2、Capan-2 和 CFPAC-1 细胞中细胞侵袭显著减少。在对微切割细胞的分析中，IDC 组织中的细胞 Insig2 mRNA 的表达水平明显高于正常胰腺细胞（P<0.001）和胰腺上皮内瘤变细胞（P=0.082）。在对 IDC 细胞的分析中，晚期患者的 Insig2 mRNA 表达水平明显高于早期患者。本数据表明，Insig2 与缺氧条件下胰腺癌的恶性潜能有关。
