Expression of vascular endothelial growth factor, mitogen-activated protein kinase and p53 in human colorectal cancer.
BACKGROUND
VEGF is a growth factor involved in the regulation of angiogenesis, a process that plays a central role in tumor growth. It has been suggested that mutations of p53 and activation of the Ras/MAPK pathway may contribute to the up-regulation of VEGF expression and induction of angiogenesis.


METHODS
We explored the expression of p53 and VEGF and p44MAPK phosphorylation in 43 human colorectal carcinomas, as well as in peritumoral mucosas, and in normal mucosas in order to establish a correlation between VEGF expression and either mutations of p53 or phosphorylation of p44MAPK. Overexpression of p53 in tumor tissues was interpreted as evidence of mutations.


RESULTS
p53 was overexpressed in 22 out of 43 tumors; MAPK was phosphorylated in 25 out of 43 cases whereas only 4 out of 22 peritumoral mucosas showed a moderate phosphorylation of p44MAPK VEGF was up-regulated in 22 out of 43 tumors, moderately expressed in 4 out of 22 peritumoral mucosas and not detectable in normal mucosa. Immunohistochemical analysis showed the presence of a phosphorylated form of p44 MAPK only in neoplastic cells. Statistical analysis demonstrated a significant correlation between p53 and VEGF expression (p<0.03) as well as between VEGF expression and p44 MAPK phosphorylation (p<0.002).


CONCLUSIONS
These data suggest that mutations of p53 and activation of the Ras/MAPK pathway may play a role in the induction of VEGF expression in human colorectal cancer.
Cassano
Alessandra
A
Institute of Internal Medicine, Unit of Medical Oncology, Catholic University, Rome, Italy.
Bagalà
Cinzia
C
Battelli
Chiara
C
Schinzari
Giovanni
G
Quirino
Michela
M
Ratto
Carlo
C
Landriscina
Matteo
M
Barone
Carlo
C
D000230:Adenocarcinoma / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000473:pathology*; D016228:Endothelial Growth Factors / Q000032:analysis*; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis*; D012004:Rectal Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020928:Mitogen-Activated Protein Kinases