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[Cancer Research 61, 462-468, January 15, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

RB2/p130 Gene-enhanced Expression Down-Regulates Vascular Endothelial Growth Factor Expression and Inhibits Angiogenesis in Vivo1

Pier Paolo Claudio, Peter Stiegler, Candace M. Howard, Cristiana Bellan, Corrado Minimo, Gian Marco Tosi, Janusz Rak, Al Kovatich, Paola De Fazio, Pietro Micheli, Mario Caputi, Lorenzo Leoncini, Robert Kerbel, Giovan Giacomo Giordano and Antonio Giordano2

Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107 [P. P. C., P. S., C. M. H., C. M., A. K., A. G.]; Dipartimento di Scienze Odontostomatologiche e Maxillo-Facciali, Universita di Napoli "Federico II," Napoli, Italy [P. P. C.]; Istituto di Anatomia Patologica e Histology [C. B., L. L.] e Dipartimento di Scienze Oftalmologiche e Neurochirurgiche [G. M. T.], Universita di Siena, Siena, Italy; Division of Cancer Biology Research, Sunnybrook Health Science, Toronto, Ontario, M4N 3M5 Canada [J. R., R. K.]; Servizio di Anatomia ed Istologia Patologica e Citologia Diagnostica, Azienda Ospedaliera "Cotugno," Napoli, Italy [P. D. F., P. M.]; Istituto di Malattie dell’Apparato Respiratorio, II Universita’ degli Studi di Napoli and Istituto di Ricerca Cardio-Pneumologico A. O. "Monaldi," Napoli, Italy [M. C.]; and Istituto di Anatomia Patologica, Facolta’ di Medicina, II Universita’ degli studi di Napoli, Napoli, Italy [G. G. G.]

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.




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Copyright © 2001 by the American Association for Cancer Research.