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Involvement of RB gene family in tumor angiogenesis

Oncogene volume 25, pages 5326–5332 (2006)Cite this article

Abstract

Angiogenesis, the development of new blood vessels from pre-existing vessels, represents a fundamental step in tumor progression and metastatization. The induction of vasculature is required for growth of the tumor mass, to ensure an adequate supply of oxygen and metabolites to the tumor beyond a critical size. Tumor angiogenesis is a highly regulated process that is controlled physiologically by the tumor microenvironment and genetically by alteration of several oncogenes or tumor suppressor genes. We will focus on recent demonstrations regarding the involvement of the retinoblastoma family proteins (phosphorylated retinoblastoma (pRb), p107 and pRb2/p130) at different levels of the angiogenic process. pRb and its homologs can regulate the expression of pro- and antiangiogenic factors, such as the vascular endothelial growth factor, through an E2F-dependent mechanism. Moreover, pRb is able to modulate also the transcriptional activity of several angiogenesis-related factors like HIF-1, Id2 and Oct-1. pRb2/p130 is required for both differentiation and mobilization of bone marrow-derived endothelial cell precursors and endothelial sprouting from neighboring vessels. The involvement of the pRb pathway in the angiogenesis process has also been demonstrated by different cellular models expressing viral oncoproteins, like human papilloma virus. Moreover, some natural and synthetic compounds demonstrate their antiangiogenetic activity with a mechanism of action involving pRb. Finally, the possible prognostic value of immunohistochemical evaluation of pRb and/or pRb2/p130 expression can represent a useful tool for the characterization of the angiogenic phenotype of specific tumor histotypes.

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Acknowledgements

We thank Dr Adele Petricca for secretarial assistance in the preparation of the manuscript and Paula Franke for revising the English language. Gabellini C is a recipient of a fellowship from Italian Foundation for Cancer Research.

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  1. Experimental Chemotherapy Laboratory, ‘Regina Elena’ Cancer Institute, Rome, Italy

    C Gabellini, D Del Bufalo & G Zupi

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  1. C Gabellini
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  2. D Del Bufalo
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  3. G Zupi
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Correspondence to G Zupi.

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Gabellini, C., Del Bufalo, D. & Zupi, G. Involvement of RB gene family in tumor angiogenesis. Oncogene 25, 5326–5332 (2006). https://doi.org/10.1038/sj.onc.1209631

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