RB2/p130 gene-enhanced expression down-regulates vascular endothelial growth factor expression and inhibits angiogenesis in vivo

Angiogenesis Is an essential step in the progression of tumor formation and development. The switch to an angiogenetic phenotype can occur as a distin ct step before progression to a neoplastic phenotype and is linked to genet ic changes such as mutations in key fell cycle regulatory genes. The pathog enesis of the angiogenetic phenotype may involve the inactivation of tumor suppressor genes such as the "guardian of the genome," p53, and the cyclin- dependent kinase inhibitor p16, Retinoblastoma family member RB2/p130 encod es a cell cycle regulatory protein and has been found mutated in different tumor types. Overexpression of RB2/p130 not only suppresses tumor formation in nude mice but also causes regression of established tumor grafts, sugge sting that RB2/p130 may modulate the angiogenetic balance,We found that ind uction of RB2/p130 expression using a tetracycline-regulated gene expressio n system as well as retroviral and adenoviral-mediated gene delivery inhibi ted angiogenesis in vivo. This correlated,vith pRb2/p130-mediated down-regu lation of vascular endothelial growth factor protein expression both ill vi tro and irt vivo.