EGF Regulation of VEGF: Role in Progression of ErbB2 Overexpressing Mammary Tumors
Abstract
Progression of breast tumors is dependent on blood vessel infiltration to supply nutrients and remove wastes. Expression of the angiogenic molecule vascular endothelial growth factor (VEGF) is a critical component of normal and pathological tissue vascularization. ErbB2, an epidermal growth factor receptor family member whose overexpression in mammary tumors is correlated with poor patient prognosis, has been previously implicated as a positive modulator of VEGF expression. I utilized a normal mouse mammary cell line (HC11) transfected with ErbB2 expression vectors to study the effects of ErbB2 overexpression on VEGF regulation. I have identified the promoter regions through which ErbB2 overexpression regulates VEGF expression by completing a structure-function analysis of the VEGF promoter in cultured mammary cells that overexpress ErbB2. ErbB2-mediated upregulation of VEGF involves at least two distinct promoter elements. One previously identified as the hypoxia responsive element and the other being the basal promoter region of the VEGF gene consisting of two adjacent SP1 transcription factor binding sites.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2004
- Accession Number
- ADA427846
Entities
People
- Patricia A. D'amore
- Robyn M. Loureiro
Organizations
- Schepens Eye Research Institute