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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Kanda
Koji
K
Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan.
Ueda
Masatsugu
M
Futakuchi
Hikari
H
Yamaguchi
Hiroyuki
H
Mori
Kuniko
K
Terai
Yoshito
Y
Ueki
Minoru
M
D042501:Angiogenic Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D010447:Peptide Hydrolases / Q000096:biosynthesis / Q000235:genetics; D020033:Protein Isoforms; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation; D002583:Uterine Cervical Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000378:metabolism; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis* / Q000235:genetics
D042501:Angiogenic Proteins; D020033:Protein Isoforms; D042582:Vascular Endothelial Growth Factor C; D010447:Peptide Hydrolases; D020778:Matrix Metalloproteinase 2