Suppressed expression of NDRG2 correlates with poor prognosis in pancreatic cancer

Akihiro Yamamura, Koh Miura, Hideaki Karasawa, Kazuhiro Morishita, Keiko Abe, Yasuhiko Mizuguchi, Yuriko Saiki, Shinichi Fukushige, Naoyuki Kaneko, Tomohiko Sase, Hiroki Nagase, Makoto Sunamura, Fuyuhiko Motoi, Shinichi Egawa, Chikashi Shibata, Michiaki Unno, Iwao Sasaki, Akira Horii

研究成果: Article査読

23 被引用数 (Scopus)

抄録

Pancreatic cancer is a highly lethal disease with a poor prognosis; the molecular mechanisms of the development of this disease have not yet been fully elucidated. N-myc downstream regulated gene 2 (NDRG2), one of the candidate tumor suppressor genes, is frequently downregulated in pancreatic cancer, but there has been little information regarding its expression in surgically resected pancreatic cancer specimens. We investigated an association between NDRG2 expression and prognosis in 69 primary resected pancreatic cancer specimens by immunohistochemistry and observed a significant association between poor prognosis and NDRG2-negative staining (P = 0.038). Treatment with trichostatin A, a histone deacetylase inhibitor, predominantly up-regulated NDRG2 expression in the NDRG2 low-expressing cell lines (PANC-1, PCI-35, PK-45P, and AsPC-1). In contrast, no increased NDRG2 expression was observed after treatment with 5-aza-2′ deoxycytidine, a DNA demethylating agent, and no hypermethylation was detected in either pancreatic cancer cell lines or surgically resected specimens by methylation specific PCR. Our present results suggest that (1) NDRG2 is functioning as one of the candidate tumor-suppressor genes in pancreatic carcinogenesis, (2) epigenetic mechanisms such as histone modifications play an essential role in NDRG2 silencing, and (3) the expression of NDRG2 is an independent prognostic factor in pancreatic cancer.

本文言語English
ページ(範囲)102-107
ページ数6
ジャーナルBiochemical and biophysical research communications
441
1
DOI
出版ステータスPublished - 2013 11 8

ASJC Scopus subject areas

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学

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