TY - JOUR
T1 - p73 overexpression increases VEGF and reduces thrombospondin-1 production
T2 - Implications for tumor angiogenesis
AU - Vikhanskaya, Faina
AU - Bani, Maria R.
AU - Borsotti, Patrizia
AU - Ghilardi, Carmen
AU - Ceruti, Roberta
AU - Ghisleni, Gabriele
AU - Marabese, Mirko
AU - Giavazzi, Raffaella
AU - Broggini, Massimo
AU - Taraboletti, Giulia
PY - 2001/11/1
Y1 - 2001/11/1
N2 - Tumor neovascularization is controlled by a balance between positive and negative effectors, whose production can be regulated by oncogenes and tumor suppressor genes. The aim of this study was to investigate whether the angiogenic potential of tumors could also be controlled by p73, a gene homologous to the tumor suppressor p53, whose involvement in tumor angiogenesis is known. We have studied the production of proangiogenic (VEGF, FGF-2, PIGF and PDGF) and antiangiogenic (TSP-1) factors in two p73 overexpressing clones obtained from the human ovarian carcinoma cells A2780. TSP-1 was downregulated in both clones compared to mock transfected cells, both at mRNA and protein level. Conversely, both clones showed an increased production of VEGF mRNA and protein. For both TSP-1 and VEGF, regulation of expression was partially due to modulation of the promoter activity, and was dependent on p53 status. Production of the other angiogenic factors FGF-2, PIGF and PDGF-B was also increased in p73 overexpressing clones. The two clones were more angiogenic than parental cells, as shown in vitro by their increased chemotactic activity for endothelial cells, and in vivo by the generation of more vascularized tumors. These findings suggest a potential role of p73 in tumor angiogenesis.
AB - Tumor neovascularization is controlled by a balance between positive and negative effectors, whose production can be regulated by oncogenes and tumor suppressor genes. The aim of this study was to investigate whether the angiogenic potential of tumors could also be controlled by p73, a gene homologous to the tumor suppressor p53, whose involvement in tumor angiogenesis is known. We have studied the production of proangiogenic (VEGF, FGF-2, PIGF and PDGF) and antiangiogenic (TSP-1) factors in two p73 overexpressing clones obtained from the human ovarian carcinoma cells A2780. TSP-1 was downregulated in both clones compared to mock transfected cells, both at mRNA and protein level. Conversely, both clones showed an increased production of VEGF mRNA and protein. For both TSP-1 and VEGF, regulation of expression was partially due to modulation of the promoter activity, and was dependent on p53 status. Production of the other angiogenic factors FGF-2, PIGF and PDGF-B was also increased in p73 overexpressing clones. The two clones were more angiogenic than parental cells, as shown in vitro by their increased chemotactic activity for endothelial cells, and in vivo by the generation of more vascularized tumors. These findings suggest a potential role of p73 in tumor angiogenesis.
KW - Angiogenesis
KW - Ovarian carcinoma
KW - p73
KW - Thrombospondin-1
KW - VEGF
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U2 - 10.1038/sj.onc.1204896
DO - 10.1038/sj.onc.1204896
M3 - Article
C2 - 11704858
AN - SCOPUS:0035504921
VL - 20
SP - 7293
EP - 7300
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 50
ER -