Ribozyme mediated suppression of vascular endothelial growth factor gene expression enhances matrix metalloproteinase 1 expression in a human hepatocellular carcinoma cell line.
The levels of expression of various genes were altered in cellular transformants with manipulation of expression of single genes. Vascular endothelial growth factor A (VEGF-A) is a key molecule for tumor progression, although it is unclear how VEGF-A expression regulates various genes. Multiple gene expression levels were evaluated using cDNA arrays in a human hepatocellular carcinoma cell line (HLF) with suppression of the VEGF-A gene by anti-VEGF-A ribozyme (alphaVRz). The ribozyme-mediated suppression of VEGF-A gene solely up-regulated matrix metalloproteinase 1 (MMP1) gene level in HLF/alphaVRz. Levels of expression of other members of MMP family or tissue inhibitors of MMPs did not show any alteration. These results suggested that intracellular suppression of VEGF-A gene was specifically linked to up-regulation of MMP1 in human hepatocellular carcinoma cells.
Kamochi
Junichiro
J
Department of Pathology, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan.
Tokunaga
Tetsuji
T
Morino
Fumitoshi
F
Nagata
Junko
J
Tomii
Yasushi
Y
Abe
Yoshiyuki
Y
Hatanaka
Hiroyuki
H
Kijima
Hiroshi
H
Yamazaki
Hitoshi
H
Watanabe
Norihito
N
Matsuzaki
Shohei
S
Ueyama
Yoshito
Y
Nakamura
Masato
M
D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016337:RNA, Catalytic / Q000494:pharmacology*; D014170:Transformation, Genetic; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A
D016228:Endothelial Growth Factors; D016337:RNA, Catalytic; D042461:Vascular Endothelial Growth Factor A; C415803:alpha VRz; D020781:Matrix Metalloproteinase 1