The interferon-inducible IFI16 gene inhibits tube morphogenesis and proliferation of primary, but not HPV16 E6/E7-immortalized human endothelial cells

Ravera Raffaella; Daniela Gioia; Marco De Andrea; Paola Cappello; Mirella Giovarelli; Peggy Marconi; Roberto Manservigi; Marisa Gariglio; Santo Landolfo

doi:10.1016/j.yexcr.2003.10.014

The interferon-inducible IFI16 gene inhibits tube morphogenesis and proliferation of primary, but not HPV16 E6/E7-immortalized human endothelial cells

Exp Cell Res. 2004 Feb 15;293(2):331-45. doi: 10.1016/j.yexcr.2003.10.014.

Authors

Ravera Raffaella¹, Daniela Gioia, Marco De Andrea, Paola Cappello, Mirella Giovarelli, Peggy Marconi, Roberto Manservigi, Marisa Gariglio, Santo Landolfo

Affiliation

¹ Department of Public Health and Microbiology, University of Turin, Via Santena 9, 10126 Turin, Italy.

PMID: 14729471
DOI: 10.1016/j.yexcr.2003.10.014

Abstract

Immunohistochemical analysis has demonstrated that the human IFI16 gene, in addition to the hematopoietic tissues, is highly expressed in endothelial cells and squamous stratified epithelia. In this study, we have developed a reliable HSV-derived replication-defective vector (TO-IFI16) to efficiently transduce IFI16 into primary human umbilical vein endothelial cells (HUVEC), which are usually poorly transfectable. HUVEC infection with TO-IFI16 virus suppressed endothelial migration, invasion and formation of capillary-like structures in vitro. In parallel, sustained IFI16 expression inhibited HUVEC cell cycle progression, accompanied by significant induction of p53, p21, and hypophosphorylated pRb. Further support for the involvement of these pathways in IFI16 activity came from the finding that infection with TO-IFI16 virus does not impair the in vitro angiogenic activity and cell cycle progression of HUVEC immortalized by HPV16 E6/E7 oncogenes, which are known to inactivate both p53 and pRb systems. This use of a reliable viral system for gene delivery into primary human endothelial cells assigns a potent angiostatic activity to an IFN-inducible gene, namely IFI16, and thus throws further light on antiangiogenic therapy employing IFNs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiogenesis Inhibitors / genetics*
Angiogenesis Inhibitors / therapeutic use
Capillaries / cytology
Capillaries / growth & development*
Capillaries / metabolism
Cell Count
Cell Cycle / genetics
Cell Division / drug effects
Cell Line, Transformed
Cell Movement / genetics
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / metabolism
Endothelial Cells / cytology
Endothelial Cells / metabolism*
Endothelial Cells / virology
Gene Expression Regulation, Neoplastic / genetics
Genetic Vectors / therapeutic use*
Humans
Interferons / metabolism
Interferons / pharmacology
Neovascularization, Pathologic / genetics*
Neovascularization, Pathologic / therapy
Nuclear Proteins*
Oncogene Proteins, Viral / genetics
Papillomavirus E7 Proteins
Phosphoproteins*
Proteins / genetics*
Proteins / therapeutic use
Repressor Proteins*
Retinoblastoma Protein / metabolism
Simplexvirus / genetics
Transduction, Genetic / methods*
Tumor Suppressor Protein p53 / metabolism

Substances

Angiogenesis Inhibitors
CDKN1A protein, human
Cyclin-Dependent Kinase Inhibitor p21
Cyclins
E6 protein, Human papillomavirus type 16
Nuclear Proteins
Oncogene Proteins, Viral
Papillomavirus E7 Proteins
Phosphoproteins
Proteins
Repressor Proteins
Retinoblastoma Protein
Tumor Suppressor Protein p53
oncogene protein E7, Human papillomavirus type 16
IFI16 protein, human
Interferons