Ladomery Lab RNA Biology Group


Ladomery Lab
Southwest UK RNA Club

Invited Reviews

Alternative splicing in angiogenesis: the vascular endothelial growth factor paradigm

Cancer Lett. 249: 133-142 (2007) - PMID: 17027147

Authors: Ladomery MR, Harper SJ, Bates DO

Abstract

Alternative splicing, first discovered in the 1970s, has emerged as one of the key generators of proteomic diversity. Not surprisingly, alternative splicing is increasingly linked to the aetiology of cancer. This is illustrated by VEGF, the dominant angiogenic factor. Recently, an antiangiogenic family of VEGF isoforms was discovered, and termed VEGFxxxb. VEGFxxxb isoforms arise from an alternative 3’ splice site in exon eight, and differ by a mere six amino-acids at the C-terminus. These alternative six amino-acids radically change the functional properties of VEGF. VEGFxxxb isoform expression is regulated in human tissues and development; and disregulated in many pathological states including cancer. Understanding what regulates VEGFxxxb alternative splicing, and therefore the balance of pro and antiangiogenic isoforms is of great importance, and will be explored in detail over the next few years.

Keywords: Alternative splicing; VEGF; angiogenesis; tumours; VEGF165b