Identification of derlin-1 as a novel growth factor-responsive endothelial antigen by suppression subtractive hybridization.
Endothelial cells play an important regulatory role in embryonic development, reproductive functions, tumor growth and progression. In the present study, the suppression subtractive hybridization (SSH) method was employed to identify differentially expressed genes between non-stimulated endothelial cells and activated endothelial cells. Following mRNA isolation of non-stimulated and hepatocellular carcinoma homogenate-stimulated cells, cDNAs of both populations were prepared and subtracted by suppressive PCR. Sequencing of the enriched cDNAs identified a couple of genes differentially expressed, including derlin-1. Derlin-1 was significantly up-regulated by tumor homogenates, VEGF, and endothelial growth supplements in a dose-dependent manner. Knock-down of derlin-1 triggered endothelial cell apoptosis, inhibited endothelial cell proliferation, and blocked the formation of a network of tubular-like structures. Our data reveal that derlin-1 is a novel growth factor-responsive endothelial antigen that promotes endothelial cell survival and growth.
Ran
Yuliang
Y
Department of Cellular and Molecular Biology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, PR China.
Jiang
Yangfu
Y
Zhong
Xing
X
Zhou
Zhuan
Z
Liu
Haiyan
H
Hu
Hai
H
Lou
Jin-Ning
JN
Yang
Zhihua
Z
D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic; D009693:Nucleic Acid Hybridization / Q000379:methods; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D000951:Antigens, Neoplasm; C487709:DERL1 protein, human; D008565:Membrane Proteins; D042461:Vascular Endothelial Growth Factor A