Transcriptional expression of the genes implicated in angiogenesis and tumor invasion in cervical carcinomas

• Published in: Gynecologic oncology 2005-09, Vol.98 (3), p.453-461
• Main Authors: Kanda, Koji, Ueda, Masatsugu, Futakuchi, Hikari, Yamaguchi, Hiroyuki, Mori, Kuniko, Terai, Yoshito, Ueki, Minoru
• Format: Article
• Language: English
• Subjects: Angiogenesis; Angiogenic Proteins - biosynthesis; Angiogenic Proteins - genetics; Cervical carcinoma; Female; Humans; Invasion; Matrix Metalloproteinase 2 - biosynthesis; Matrix Metalloproteinase 2 - genetics; MMP-2; Neoplasm Invasiveness; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - metabolism; Peptide Hydrolases - biosynthesis; Peptide Hydrolases - genetics; Protein Isoforms; Reverse Transcriptase Polymerase Chain Reaction; Transcriptional Activation; Uterine Cervical Neoplasms - blood supply; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - metabolism; Vascular Endothelial Growth Factor C - biosynthesis; Vascular Endothelial Growth Factor C - genetics; VEGF-C
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2005.05.005

Co-expression patterns of the genes implicated in angiogenesis and tumor invasion in cervical carcinoma cells were investigated together with invasive activity of tumor cells. Transcript levels of those genes were also compared between tumor cells and normal cervical tissues. Real-time quantitative RT-PCR analysis was conducted on selected 11 genes (total VEGF-A, VEGF 121, VEGF 165, VEGF 189, VEGF-B, C and D, bFGF, dThdPase, MMP-2 and uPA) using 11 cervical carcinoma cell lines and 14 normal cervical tissues. Protein expression of VEGF-C and MMP-2 and invasive activity of tumor cells were evaluated for each cell line by sandwich ELISA and haptoinvasion assay, respectively. Gene co-expression analysis revealed the significant correlation between angiogenic factors and proteinases in malignant but not in normal cervical samples. Gene or protein expression levels of VEGF-C and MMP-2 were well correlated with the number of invaded tumor cells. VEGF-A splicing variants were increased in malignant compared to normal cervical samples but not associated with the invasive activity of the cells. VEGF-C and MMP-2 were closely related to invasive phenotype of tumor cells, whereas VEGF-A isoforms were considered to be involved in cervical carcinogenesis.