Expression of vascular endothelial growth factor and its receptors KDR and Flt-1 in gastric cancer cells.
OBJECTIVE
The expression of vascular endothelial growth factor (VEGF) and its receptors KDR and Flt-1 by gastric carcinoma tissues and different gastric carcinoma cell lines was detected to elucidate the molecular mechanism of this growth factor in promoting tumor growth.


METHODS
The expression of VEGF, Flt-1 and KDR was determined by reverse transcription-polymerase chain reaction (RT-PCR) in gastric cancer cell lines RF-1, RF-48, AGS-1, NCI-N87, NCI-SNU-1, NCI-SNU-5, NCI-SNU-16 and KATO-III. The expression of Flt-1 and KDR in paraffin-embedded specimens of gastric cancer was determined by immunohistochemistry. The 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was used to assess the role of VEGF in tumor cell proliferation.


RESULTS
All 8 gastric cancer cell lines analyzed expressed VEGF(121) and VEGF(165) and six of them expressed both Flt-1 and KDR, while cell line NCI-SNU-5 expressed Flt-1 only and cell line KATOIII expressed neither Flt-1 nor KDR. The gastric carcinoma tissues expressed Flt-1 and KDR widely, with the positive rate of expression of Flt-1 and KDR being 84.6 % and 70 % respectively. The exogenous VEGF stimulated the growth of KDR-positive cell lines NCI-N87 and AGS-1 in a dose-dependent manner but exhibited no effect on the growth of KDR-negative cell line NCI-N87.


CONCLUSIONS
VEGF and its receptors KDR and Flt-1 were expressed widely in gastric carcinoma cells and the VEGF stimulated KDR-positive tumor cell growth directly. These results suggest that VEGF may play a role in promoting tumor growth and metastasis by participating in both paracrine and autocrine pathways.
Zhang
Hua
H
Department of Biochemistry and Molecular Biology, Peking University School of Oncology, Beijing Institute for Cancer Research, China.
Wu
Jian
J
Meng
Lin
L
Shou
Cheng-Chao
CC
D002455:Cell Division / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D008222:Lymphokines / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics* / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000378:metabolism*; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2