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

Madhusudhanan Narasimhan; Rajiv Rose; Ramugounder Ramakrishnan; Jason A. Zell; Appu Rathinavelu

doi:10.1016/j.lfs.2008.04.004

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

Madhusudhanan Narasimhan
, Rajiv Rose
, Ramugounder Ramakrishnan
, Jason A. Zell
, Appu Rathinavelu

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1231-1241
Number of pages	11
Journal	Life Sciences
Volume	82
Issue number	25-26
DOIs	https://doi.org/10.1016/j.lfs.2008.04.004
State	Published - Jun 20 2008

Funding

This study was supported by the grants from the Department of Education, State of Florida, made through the Center of Excellence for Marine Biology and Biotechnology at Florida Atlantic University, the Presidents Faculty Research and Development Grant of Nova Southeastern University, Florida, and the Royal Dames of Cancer Research Inc., Fort Lauderdale, Florida.

ASJC Scopus Subject Areas

General Biochemistry,Genetics and Molecular Biology
General Pharmacology, Toxicology and Pharmaceutics

Keywords

Hdm2 + VEGF
VEGF + GI-101A
VEGF + HL-60
VEGF + HUVEC
VEGF expression

Disciplines

Biochemistry, Biophysics, and Structural Biology
Pharmacology, Toxicology and Environmental Health

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10.1016/j.lfs.2008.04.004

Cite this

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title = "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.",

keywords = "Hdm2 + VEGF, VEGF + GI-101A, VEGF + HL-60, VEGF + HUVEC, VEGF expression",

author = "Madhusudhanan Narasimhan and Rajiv Rose and Ramugounder Ramakrishnan and Zell, \{Jason A.\} and Appu Rathinavelu",

year = "2008",

month = jun,

day = "20",

doi = "10.1016/j.lfs.2008.04.004",

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T1 - Identification of HDM2 as a regulator of VEGF expression in cancer cells

AU - Narasimhan, Madhusudhanan

AU - Rose, Rajiv

AU - Ramakrishnan, Ramugounder

AU - Zell, Jason A.

AU - Rathinavelu, Appu

PY - 2008/6/20

Y1 - 2008/6/20

N2 - 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.

AB - 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.

KW - Hdm2 + VEGF

KW - VEGF + GI-101A

KW - VEGF + HL-60

KW - VEGF + HUVEC

KW - VEGF expression

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

Abstract

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Keywords

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