Transcriptional Regulation of VEGF Expression in Breast Cancer
Abstract
To identify promoter elements and transcription factors that contribute to enhanced expression of Vascular Endothelial Growth Factor (VEGF) in breast cancer, reporter constructs, encompassing nested deletions approximately every 100 base pairs (bp) of the wild type (wt)-promoter (-1175 to +50) were synthesized and screened for activity by transient transfection in human breast cancer and mom-mammary cells. In most cells, a drop of > 40% in transcriptional activity was observed under normoxic conditions when sequences between positions -1175 and -1010 were deleted. Sequences downstream of the hypoxia-regulatory element (HRE) at position -971 modulate activity in a tissue- and cell type-specific manner: deletion of sequences between positions -900 and -790 reduces promoter activity another 30%, indicating differences in transcriptional regulation among tissues and within the same cell type. Electrophoretic mobility shift assays (EMSA) revealed that transcription factor Spl, but not AP-2 or Egr-1, binds the basal promoter element upstream of the transcriptional start site between positions -85 and -50.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA417429
Entities
People
- Sebastian Bredow
Organizations
- Lovelace Foundation