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

• Published in: Cancer research (Chicago, Ill.) Vol. 61; no. 2; pp. 462 - 468
• Main Authors: CLAUDIO, Pier Paolo, STIEGLER, Peter, CAPUTI, Mario, LEONCINI, Lorenzo, KERBEL, Robert, GIORDANO, Giovan Giacomo, GIORDANO, Antonio, HOWARD, Candace M, BELLAN, Cristiana, MINIMO, Corrado, TOSI, Gian Marco, RAK, Janusz, KOVATICH, Al, DE FAZIO, Paola, MICHELI, Pietro
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.01.2001
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Blotting, Northern; Cell Line; Chemotherapy; Down-Regulation; Endothelial Growth Factors - analysis; Endothelial Growth Factors - genetics; Female; Gene Expression Regulation; Genetic Therapy; Humans; Immunochemistry; Lymphokines - analysis; Lymphokines - genetics; Medical sciences; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms, Experimental - blood supply; Neoplasms, Experimental - genetics; Neoplasms, Experimental - therapy; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - therapy; p300 protein; Pharmacology. Drug treatments; Phosphoproteins - analysis; Phosphoproteins - genetics; Platelet Endothelial Cell Adhesion Molecule-1 - analysis; Proteins; RB2 gene; Retinoblastoma-Like Protein p130; RNA - genetics; RNA - metabolism; Transplantation, Heterologous; Tumor Cells, Cultured; vascular endothelial growth factor; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Antineoplastic agent; Angiogenic factor; Gene product; Gene overexpression; Angiogenesis; Transfection; Established cell line; Tumor progression; Multigene family; Mechanism of action; Vector; Tumor cell; Tumor suppressor gene; Retinoblastoma gene; Rodentia; Malignant tumor; Gene expression; In vitro; Biological activity; In vivo; Vertebrata; Mammalia; Vascular endothelium growth factor; Mouse; Animal
• ISSN: 0008-5472

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 "guardian of the genome," p53, and the cyclin-dependent kinase inhibitor p16. Retinoblastoma family member RB2/p130 encodes 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, 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 protein expression both in vitro and in vivo.