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Identification of HDM2 as a regulator of VEGF expression in cancer cells.

Abstract：

:Overexpression of vascular endothelial growth factor (VEGF) and the extent of neoangiogenesis are closely correlated with tumor development and cancer metastases. To assess whether VEGF mediated angiogenesis is regulated by HDM2, we treated the GI-101A and HL-60 cells with HDM2 gene specific antisense phosphorothioate oligodeoxynucleotide (AS5). The antisense treatment resulted in a significant reduction of both basal as well as phorbol 12,13-dibutyrate (PDB) and Diethylstilbestrol (DES) induced VEGF mRNA and protein expressions. Furthermore, when the Human Umbilical Vein Endothelial Cells (HUVECs) were exposed to medium obtained from AS5 transfected GI-101A and HL-60 cells, the angiogenesis was significantly reduced compared to the controls in the in vitro angiogenesis assay. On the contrary, the medium obtained from PDB treated cells that expressed HDM2 and VEGF at a higher level showed an increase in the tube formation by HUVEC. Thus, our present study suggests that modulation of HDM2 expression could play an important role in tumor angiogenesis and the metastatic process via transcriptional regulation of VEGF.

journal_name

Life Sci

journal_title

Life sciences

authors

Narasimhan M,Rose R,Ramakrishnan R,Zell JA,Rathinavelu A

doi

10.1016/j.lfs.2008.04.004

subject

Has Abstract

pub_date

2008-06-20 00:00:00

pages

1231-41

issue

25-26

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(08)00159-8

journal_volume

82

pub_type

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