Downmodulation of bFGF-binding protein expression following restoration of p53 function.
Angiogenesis is a requirement for solid tumor growth. Therefore, inhibition of this neovascularization is one mechanism by which restoration of wtp53 function may lead to tumor regression. Here we report that adenoviral vector-mediated wild-type p53 transduction results in growth inhibition of squamous cell carcinoma of the head and neck tumor cells both in vitro and in a xenograft mouse model. This growth inhibition is associated with the down-regulation of the expression of fibroblast growth factor binding protein, a secreted protein required for the activation of angiogenic factor basic FGF. These findings suggest that wtp53-induced tumor regression is due, at least in part, to antiangiogenesis mediated by the downmodulation of fibroblast growth factor binding protein.
Sherif
Z A
ZA
Department of Oncology, Lombardi Cancer Center, Georgetown University Medical Center, Washington, District of Columbia 20007, USA.
Nakai
S
S
Pirollo
K F
KF
Rait
A
A
Chang
E H
EH
D000256:Adenoviridae; D000818:Animals; D015152:Blotting, Northern; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000235:genetics; D003094:Collagen / Q000737:chemistry; D017931:DNA Primers / Q000737:chemistry; D015536:Down-Regulation / Q000502:physiology*; D004338:Drug Combinations; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007797:Laminin / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology; D011509:Proteoglycans / Q000737:chemistry; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D017931:DNA Primers; D004338:Drug Combinations; C489453:Fgfbp1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007797:Laminin; D011509:Proteoglycans; D016159:Tumor Suppressor Protein p53; C059485:matrigel; C070699:FGFBP1 protein, human; D012313:RNA; D003094:Collagen