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Synergistic up-regulation of Hexokinase-2, glucose transporters and angiogenic factors in pancreatic cancer cells by glucose deprivation and hypoxia

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Title: Synergistic up-regulation of Hexokinase-2, glucose transporters and angiogenic factors in pancreatic cancer cells by glucose deprivation and hypoxia
Authors: Natsuizaka, Mitsuteru Browse this author
Ozasa, Mariko Browse this author
Darmanin, Stephanie Browse this author
Miyamoto, Masaki Browse this author
Kondo, Satoshi Browse this author
Kamada, Suguru Browse this author
Shindoh, Masanobu Browse this author
Higashino, Fumihiro Browse this author
Suhara, Wakako Browse this author
Koide, Hideyuki Browse this author
Aita, Kiyoshi Browse this author
Nakagawa, Koji Browse this author
Kondo, Takeshi Browse this author →KAKEN DB
Asaka, Masahiro Browse this author
Okada, Futoshi Browse this author
Kobayashi, Masanobu Browse this author
Keywords: Hypoxia
HIF
AMPK
Glucose deprivation
Issue Date: 10-Sep-2007
Publisher: Elsevier Inc.
Journal Title: Experimental Cell Research
Volume: 313
Issue: 15
Start Page: 3337
End Page: 3348
Publisher DOI: 10.1016/j.yexcr.2007.06.013
PMID: 17651733
Abstract: There is accumulating evidence demonstrating that HIF-1 functions as a key regulator of the adaptation responses to hypoxia in cancer tissues. To this evidence, we add that adaptation responses to glucose deprivation plus hypoxia are also necessary for the survival of tumor cells in the tumor microenvironment as cancer tissues are exposed to glucose deprivation as well as hypoxia. We found that adrenomedullin (AM), VEGF, Glut-1, Glut-3, and Hexokinase-2 among 45 hypoxia-inducible genes investigated were expressed at higher levels under glucose-deprived hypoxic conditions than under hypoxic conditions. Glucose deprivation activated the AMPK under normoxia and hypoxia. Compound C, an inhibitor of AMPK, suppressed the expressions of AM and VEGF which had already been enhanced under glucose-deprived hypoxic conditions. siRNAs for both AMPKα1 and AMPKα2 suppressed the expressions of AM and VEGF. HIF-1α protein level and the transcriptional activity of HIF-1 under glucose-deprived hypoxic conditions were thus found to be similar to those under hypoxic conditions. Furthermore, tumor cells in 15 out of 20 human pancreatic cancer tissue specimens were stained by anti-phospho-AMPKα antibody. Our results thus suggest that the enhanced expressions of those genes mediated by the activation of AMPK and HIF-1 therefore play a pivotal role in the tumor formation of pancreatic cancers.
Relation: http://www.sciencedirect.com/science/journal/00144827
Type: article (author version)
URI: http://hdl.handle.net/2115/29921
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 小林 正伸

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