The secreted mitogen vascular endothelial growth factor, VEGF, plays a pivotal 
role in angiogenesis. Hypoxia, inactivation of p53 and oncogenic K-Ras induce 
VEGF expression. Other factors such as p73 may also affect VEGF levels. 
Curiously, p73 may also regulate angiogenesis by affecting the expression of the 
pigment epithelium-derived factor, PEDF. Additionally, VEGF might harbor 
additional functions through the activation of E2F transcription factors. 
Recently, a new VEGF variant formed by alternative splicing, VEGF(165)b, has 
been described as exerting anti-angiogenic activity. We study here whether p73 
isoforms levels -TAp73 and DeltaTAp73- and p53 and K-Ras status affect the 
expression of the above-mentioned angiogenesis-related genes (through the 
correlation between their expressions), the prognostic value of VEGF(165)b and 
PEDF and the correlation between VEGF and E2F-1 levels. Tumor and normal tissue 
of 112 colorectal cancer patients was analyzed to evaluate: (i) levels of TAp73, 
DeltaTAp73, VEGF, VEGF(165)b, PEDF and E2F-1 by quantitative real-time RT-PCR, 
(ii) p53 status by immunohistochemistry and (iii) mutations in the first exon of 
K-Ras by PCR-SSCP. Tumor characteristics were examined in each patient. 
Associations were observed between: (i) specific p73 isoforms and VEGF and 
VEGF(165)b expression; (ii) DeltaEx2p73 variant and downregulation of PEDF; 
(iii) VEGF and PEDF expression; (iv) inactive p53 and VEGF(165)b levels; (v) 
oncogenic K-Ras and PEDF downregulation; (vi) E2F-1 and VEGF expressions; (vii) 
VEGF(165)b downregulation and poor prognosis parameters of tumors. We conclude 
that the levels of p73 isoforms could affect the expression of VEGF, VEGF(165)b 
and PEDF. This scenario becomes complicated because a feedback between VEGF and 
PEDF may exist. VEGF may activate the E2F-1 factor. Mutations in K-Ras could 
negatively regulate PEDF expression. p53 inactivation might result in 
compensatory mechanisms such as over-expression of VEGF(165)b. Our data support 
the role of VEGF(165)b as a tumor suppressor factor in colorectal carcinogenesis 
and its possible prognosis value.