Analysis of the expression of pro- and anti-angiogenic isoforms of VEGF gene and splicing control in breast cancer

• Grant number: 09/17649-4
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: March 01, 2010
• End date: August 31, 2013
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Eny Maria Goloni Bertollo
• Grantee: Rodrigo Castro
• Host Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil

Abstract

Tumor growth and progression depend on angiogenesis, the growth of new blood vessels from a pre-existing vascular endothelium. The Vascular Endothelium Growth Factor (VEGF) is a potent endothelial cell mitogen. Increased VEGF expression is associated with tumor growth and metastasis. Nevertheless, 3' alternative splice site selection in exon 8 of VEGF gene results in a sister family of isoforms, VEGFxxxb, which are anti-angiogenic and downregulated in tumor tissues. This work aims at quantitatively analyzing the expression of pro-angiogenic and anti-angiogenic VEGF isoforms in 50 breast carcinoma and adjacent normal tissue samples and at determining the effect of regulatory proteins in the control of VEGF gene splicing. For that purpose, mRNA levels of the isoforms VEGF165 and VEGF165b of the splicing regulatory proteins SRp55, SRp40, ASF/SF2 and SRPK1 will be quantified by Real-Time PCR. The understanding of splicing-led changes on VEGF properties might expand the view on blood vessels growth in normal tissues and in pathological situations like cancer. Moreover, the manipulation of VEGF splicing control - in order to promote the selection of the distal splicing site (anti-angiogenic) instead of the proximal site (pro-angiogenic) - might promote an efficient therapy for breast cancer. (AU)