Characterization of the expression of the hypoxia-induced genes neuritin, TXNIP and IGFBP3 in cancer.
By triggering an adaptive response to hypoxia which is a common feature of tumor microenvironments, endothelial cells contribute to the onset of angiogenic responses involved in tumor growth. Therefore, identifying hypoxic markers represent a challenge for a better understanding of tumor angiogenesis and for the optimization of anti-angiogenic therapeutic strategy. Using representational difference analysis combined with microarray, we here report the identification of 133 hypoxia-induced transcripts in human microendothelial cells (HMEC-1). By Northern blot, we confirm hypoxia-induced expression of insulin-like growth factor binding protein 3 (igfbp3), thioredoxin-interacting protein (txnip), neuritin (nrn1). Finally, by performing in situ hybridization on several types of human tumors, we provide evidence for nrn1 and txnip as hypoxic perinecrotic markers and for igfbp3 as a tumor endothelial marker. We propose these hypoxia-induced genes could represent relevant prognostic tools and targets for therapeutic intervention in cancers.
Le Jan
Sébastien
S
INSERM, Unit 36, Paris, France.
Le Meur
Nolwenn
N
Cazes
Aurélie
A
Philippe
Josette
J
Le Cunff
Martine
M
Léger
Jean
J
Corvol
Pierre
P
Germain
Stéphane
S
D002352:Carrier Proteins / Q000235:genetics*; D002478:Cells, Cultured; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D017403:In Situ Hybridization; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D009479:Neuropeptides / Q000235:genetics*; D013879:Thioredoxins / Q000235:genetics*
D002352:Carrier Proteins; D058851:GPI-Linked Proteins; D018972:Insulin-Like Growth Factor Binding Protein 3; C484539:NRN1 protein, human; D009479:Neuropeptides; C486715:TXNIP protein, human; D013879:Thioredoxins