TY - JOUR
T1 - Suppressed expression of NDRG2 correlates with poor prognosis in pancreatic cancer
AU - Yamamura, Akihiro
AU - Miura, Koh
AU - Karasawa, Hideaki
AU - Morishita, Kazuhiro
AU - Abe, Keiko
AU - Mizuguchi, Yasuhiko
AU - Saiki, Yuriko
AU - Fukushige, Shinichi
AU - Kaneko, Naoyuki
AU - Sase, Tomohiko
AU - Nagase, Hiroki
AU - Sunamura, Makoto
AU - Motoi, Fuyuhiko
AU - Egawa, Shinichi
AU - Shibata, Chikashi
AU - Unno, Michiaki
AU - Sasaki, Iwao
AU - Horii, Akira
N1 - Funding Information:
We are grateful to Dr. Barbara Lee Smith Pierce (University of Maryland University College) for editorial work in the preparation of this manuscript, to Naomi Kanai, Emiko Kondo, Emiko Shibuya, Midori Chiba, and Keiko Inabe for excellent technical assistance, and to Biomedical Research Core (Tohoku University School of Medicine) for technical support. This work was supported in part by Grants-in-Aid (Grant #17015003, 22591512, and 23590452) and by the Academic Frontier Project for Private Universities: matching fund subsidy 2006–2010 from the Ministry of Education, Culture, Sports, Science and Technology of Japan, a Grant-in-Aid for Cancer Research (Grant #18–19) from the Ministry of Health, Labour and Welfare of Japan, Pancreas Research Foundation of Japan, and Gonryo Medical Foundation.
PY - 2013/11/8
Y1 - 2013/11/8
N2 - 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.
AB - 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.
KW - Epigenetic silencing
KW - Hypermethylation
KW - NDRG2
KW - Pancreatic cancer
KW - Prognostic factor
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U2 - 10.1016/j.bbrc.2013.10.010
DO - 10.1016/j.bbrc.2013.10.010
M3 - Article
C2 - 24134849
AN - SCOPUS:84887471579
SN - 0006-291X
VL - 441
SP - 102
EP - 107
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -
