Insig2 is overexpressed in pancreatic cancer and its expression is induced by hypoxia

Tadashi Kayashima, Kohei Nakata, Kenoki Ohuchida, Junji Ueda, Kengo Shirahane, Hayato Fujita, Lin Cui, Kazuhiro Mizumoto, Masao Tanaka

研究成果: ジャーナルへの寄稿記事

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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.

元の言語英語
ページ(範囲)1137-1143
ページ数7
ジャーナルCancer Science
102
発行部数6
DOI
出版物ステータス出版済み - 6 1 2011

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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