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学科主题基础医学
Relevance of amyloid precursor-like protein 2 C-terminal fragments in pancreatic cancer cells
Peters, Haley L.1; Tuli, Amit1,2; Wang, Xiaojian1; Liu, Cuiling3,4; Pan, Zenggang5; Ouellette, Michel M.1,2; Hollingsworth, Michael A.1,3; MacDonald, Richard G.1,2; Solheim, Joyce C.1,2,3
关键词amyloid precursor protein amyloid precursor-like protein 2 beta-site APP cleaving enzyme pancreatic cancer
刊名INTERNATIONAL JOURNAL OF ONCOLOGY
2012-10-01
DOI10.3892/ijo.2012.1553
41期:4页:1464-1474
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]CHONDROITIN SULFATE GLYCOSAMINOGLYCAN ; ALZHEIMERS-DISEASE ; TOLFENAMIC ACID ; DUCTAL ADENOCARCINOMA ; EPITHELIAL-CELLS ; LINE SUIT-2 ; HUMAN BACE2 ; APP FAMILY ; BETA-SITE ; SECRETASE
英文摘要

In some cellular systems, particularly neurons, amyloid precursor-like protein 2 (APLP2), and its highly homologous family member amyloid precursor protein (APP), have been linked to cellular growth. APLP2 and APP undergo regulated intramembrane proteolysis to produce C-terminal fragments. In this study, we found comprehensive expression of APLP2 C-terminal fragments in a panel of pancreatic cancer cell lines; however, APP C-terminal fragments were notably limited to the BxPC3 cell line. Extensive glycosaminoglycan modification on APLP2 was also found in the majority of pancreatic cancer cell lines. Glycosaminoglycan-modified and -unmodified APLP2, and particularly APLP2 C-terminal fragments, also demonstrated increased expression in oncogene-transformed pancreatic ductal cells. Additionally, elevated APLP2 levels were confirmed in human pancreatic cancer tissue. Downregulation of APLP2 and APP expression, alone or in combination, caused a decrease in the growth of a pancreatic cancer cell line with representatively low APP C-terminal fragment expression, the S2-013 cell line. Furthermore, we found that treatment with beta-secretase inhibitors to block formation of APLP2 C-terminal fragments decreased the growth and viability of S2-013 cells, without affecting the survival of a non-transformed pancreatic ductal cell line. In conclusion, our studies demonstrate that abundant APLP2, but not APP, C-terminal fragment expression is conserved in pancreatic cancer cell lines; however, APP and APLP2 equally regulated the growth of S2-013 pancreatic cancer cells. Chiefly, our discoveries establish a role for APLP2 in the growth of pancreatic cancer cells and show that inhibitors preventing APLP2 cleavage reduce the viability of pancreatic cancer cells.

语种英语
WOS记录号WOS:000309297900033
项目编号P50CA127297 ; 5P20RR018759-10 ; 8P20GM103489-10 ; R01 GM57428 ; T32 CA009476 ; P30CA036727
资助机构NIH SPORE ; NIH/NCRR COBRE from National Center for Research Resources ; National Institute of General Medicine Sciences ; NIH ; Nebraska Department of Health and Human Services Award ; University of Nebraska Medical Center Graduate Studies Emley and Regents Tuition Fellowships ; NIH Training Grant ; Graduate Assistance in Areas of National Need Fellowship ; University of Nebraska Graduate Studies Assistantship ; Department of Science and Technology, Government of India ; NIH Cancer Center
引用统计
被引频次:8[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50770
专题北京大学基础医学院_病理学系
北京大学基础医学院
作者单位1.Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA
2.Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA
3.Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA
4.Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100191, Peoples R China
5.City Hope Natl Med Ctr, Div Pathol, Duarte, CA 91010 USA
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GB/T 7714
Peters, Haley L.,Tuli, Amit,Wang, Xiaojian,et al. Relevance of amyloid precursor-like protein 2 C-terminal fragments in pancreatic cancer cells[J]. INTERNATIONAL JOURNAL OF ONCOLOGY,2012,41(4):1464-1474.
APA Peters, Haley L..,Tuli, Amit.,Wang, Xiaojian.,Liu, Cuiling.,Pan, Zenggang.,...&Solheim, Joyce C..(2012).Relevance of amyloid precursor-like protein 2 C-terminal fragments in pancreatic cancer cells.INTERNATIONAL JOURNAL OF ONCOLOGY,41(4),1464-1474.
MLA Peters, Haley L.,et al."Relevance of amyloid precursor-like protein 2 C-terminal fragments in pancreatic cancer cells".INTERNATIONAL JOURNAL OF ONCOLOGY 41.4(2012):1464-1474.
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