RB2/p130 gene-enhanced expression downregulates vascular endothelial growth factor expression and inhibits angiogenesis in vivo
A. A. Mancini, G. G. Marsico, P. P. P. P. Claudio, A. A. Di Sorbo, C. C. Petagna, A. A. Giordano, M. M. Caputi (Naples, Italy; Philadelphia, United States Of America)
Source: Annual Congress 2002 - Thoracic oncology: biology
Session: Thoracic oncology: biology
Session type: Oral Presentation
Number: 141
Disease area: Thoracic oncology
Abstract The retinoblastoma (Rb) family consists of the tumor suppressor pRb/p105 and related proteins p107 and pRb2/p130. Recent studies showed that tumors transduced with the RB2/p130 retrovirus showed some calcifications and internal necrosis. This data led us to study the possible relation between pRb2/p130 in vivo overexpression and angiogenesis. Angiogenesis is an essential step in the progression of tumor formation and development. The switch to an angiogenetic phenotype can occur as a distinct step before progression to a neoplastic phenotype and is linked to genetic changes such as mutations in key cell cycle regulatory genes. The pathogenesis of the angiogenetic phenotype may involve the inactivation of tumor suppressor genes such as the [dsquote]guardian of the genome,[dsquote] p53, and the cyclin dependent kinase inhibitor p16. Overexpression of RB2/p130 not only suppresses tumor formation in nude mice but also causes regression of established tumor grafts, suggesting that RB2/p130 may modulate the angiogenetic balance. We found that induction of RB2/p130 expression using a tetracycline-regulated gene expression system as well as retroviral and adenoviral-mediated gene delivery inhibited angiogenesis in vivo. This correlated with pRb2/p130-mediated down-regulation of vascular endothelial growth factor (VEGF) protein expression both in vitro and in vivo.
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A. A. Mancini, G. G. Marsico, P. P. P. P. Claudio, A. A. Di Sorbo, C. C. Petagna, A. A. Giordano, M. M. Caputi (Naples, Italy; Philadelphia, United States Of America). RB2/p130 gene-enhanced expression downregulates vascular endothelial growth factor expression and inhibits angiogenesis in vivo . Eur Respir J 2002; 20: Suppl. 38, 141
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