Identification of genes differentially induced by hypoxia in pancreatic cancer cells.
A hypoxic microenvironment is characteristic of many solid tumors, including pancreatic cancer, the fifth leading cause of cancer death in the United States. Hypoxia causes the stabilization of the HIF-1 (hypoxia-inducible factor-1) transcription factor and the induction of many genes that promote angiogenesis, tumor growth, and metastasis. We performed representational difference analysis (RDA) using mRNA extracted from hypoxic and normoxic Capan-2, a human pancreatic cancer cell line. cDNAs corresponding to hypoxia-inducible genes were cloned and sequenced. We identified GPI/NLK/AMF (glucose phosphate isomerase/neuroleukin/autocrine motility factor) as a hypoxic inducible gene. In addition, hexokinase II and DEC1/Stra13, genes known to be hypoxia inducible in other systems, were found to be hypoxia inducible in our pancreatic cancer system. We thus identified three genes that are induced by hypoxia in a human pancreatic cancer, including GPI/NLK/AMF, which was not previously known to be hypoxia inducible in any other system. These genes may provide new targets for diagnosis and treatment of pancreatic cancer.
Yoon
D Y
DY
Department of Pathology, University of California, Los Angeles 90095, USA.
Buchler
P
P
Saarikoski
S T
ST
Hines
O J
OJ
Reber
H A
HA
Hankinson
O
O
D051792:Basic Helix-Loop-Helix Proteins; D015687:Cell Hypoxia / Q000187:drug effects / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005956:Glucose-6-Phosphate Isomerase / Q000235:genetics; D006593:Hexokinase / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D005956:Glucose-6-Phosphate Isomerase; D006593:Hexokinase; D018398:Homeodomain Proteins; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D010100:Oxygen; D012333:RNA, Messenger; D014157:Transcription Factors; C107989:BHLHE40 protein, human; C497442:HIF1A protein, human