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. PATIENTS AND 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). CONCLUSION: 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.
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. PATIENTS AND METHODS: We explored the expression of p53 and VEGF and p44MAPK phosphorylation in 43 humancolorectal 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 p44MAPKVEGF 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). CONCLUSION: 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 humancolorectal cancer.
Authors: Elinne Becket; Sameer Chopra; Christopher E Duymich; Justin J Lin; Jueng Soo You; Kurinji Pandiyan; Peter W Nichols; Kimberly D Siegmund; Jessica Charlet; Daniel J Weisenberger; Peter A Jones; Gangning Liang Journal: Cancer Res Date: 2016-01-12 Impact factor: 12.701
Authors: M Landriscina; G Schinzari; G Di Leonardo; M Quirino; A Cassano; E D'Argento; L Lauriola; M Scerrati; I Prudovsky; C Barone Journal: J Neurooncol Date: 2006-06-14 Impact factor: 4.130
Authors: S J An; Y S Huang; Z H Chen; J F Han; J J Yang; Q Zhou; Z Xie; Y Yang; H H Yan; Y L Wu Journal: Cancer Gene Ther Date: 2014-02-28 Impact factor: 5.987