In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 67, No. 18 ( 2007-09-15), p. 8736-8741
Abstract:
Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis. Although many positive regulators of VEGF have been identified, relatively little is known regarding the negative regulation of VEGF expression. We identified a zinc finger transcription factor, ZNF24, that may repress VEGF transcription. An inverse correlation between expression of VEGF and ZNF24 was observed in a series of independent studies. ZNF24 was up-regulated in angiogenic tumor nodules where VEGF expression is significantly decreased compared with preangiogenic nodules. In human breast carcinoma cells cultured under normoxic conditions, ZNF24 levels were significantly up-regulated whereas VEGF levels were low. In contrast, VEGF was significantly increased in hypoxic cells whereas ZNF24 was down-regulated. The same inverse correlation between ZNF24 and VEGF was also observed in 70% of matched cDNA pairs of normal and malignant tissues from human colon and breast biopsies. Overexpression of ZNF24 resulted in a significant down-regulation of VEGF, whereas silencing of ZNF24 with small interfering RNA led to increased VEGF expression. Cotransfection of ZNF24 and a VEGF promoter luciferase reporter construct in MDA-MB-231 cells resulted in a significant decrease in VEGF promoter activity. Taken together, these data suggest that ZNF24 is involved in negative regulation of VEGF and may represent a novel repressor of VEGF transcription. [Cancer Res 2007;67(18):8736–41]
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/0008-5472.CAN-07-1617
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2007
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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