Suppressed expression of NDRG2 correlates with poor prognosis in pancreatic cancer
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- 作者：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
- 关键词：NDRG2 ; N-myc downstream regulated gene 2 ; 5-aza-dC ; 5-aza-2&prime ; deoxycytidine ; TSA ; trichostatin A ; qRT-PCR ; quantitative reverse transcription polymerase chain reaction ; cDNA ; complementary DNA ; AU ; arbitrary unit ; B2M ; 尾2-microglobulin ; MSP ; methylation-specific PCR ; HDAC ; histone deacetylase
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：8 November, 2013
- 年：2013
- 卷：441
- 期：1
- 页码：102-107
- 全文大小：1232 K
文摘
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鈥?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.