World journal of gastroenterology · 2010
Association of glypican-3 expression with growth signaling molecules in hepatocellular carcinoma.
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Akutsu Noriyuki, Yamamoto Hiroyuki, Sasaki Shigeru, Taniguchi Hiroaki, Arimura Yoshiaki, Imai Kohzoh, Shinomura Yasuhisa
Аннотация
AIM: To clarify the association of glypican-3 (GPC3) expression with Wnt and other growth signaling molecules in hepatocellular carcinoma (HCC).
METHODS: Expression of GPC3, Wnt, matrix metalloproteinases (MMPs), sulfatase (SULF)1, SULF2, and other growth signaling molecules was analyzed in HCC cell lines and tissue samples by real-time reverse transcription-polymerase chain reaction, immunoblotting, and/or immunostaining. Expression of various genes in GPC3 siRNA-transfected HCC cells was analyzed.
RESULTS: GPC3 was overexpressed in most HCCs at mRNA and protein levels and its serum levels were significantly higher in patients with HCC than in non-HCC subjects (P < 0.05). Altered expressions of various MMPs and growth signaling molecules, some of which were correlated with GPC3 expression, were observed in HCCs. Down-regulation of GPC3 expression by siRNA in GPC3-overexpressing HCC cell lines resulted in a significant decrease in expressions of MMP2, MMP14, fibroblast growth factor receptor 1, insulin-like growth factor 1 receptor. GPC3 expression was significantly correlated with nuclear/cytoplasmic localization of beta-catenin.
CONCLUSION: These results suggest that GPC3, in conjunction with MMPs and growth signaling molecules, might play an important role in the progression of HCC.
METHODS: Expression of GPC3, Wnt, matrix metalloproteinases (MMPs), sulfatase (SULF)1, SULF2, and other growth signaling molecules was analyzed in HCC cell lines and tissue samples by real-time reverse transcription-polymerase chain reaction, immunoblotting, and/or immunostaining. Expression of various genes in GPC3 siRNA-transfected HCC cells was analyzed.
RESULTS: GPC3 was overexpressed in most HCCs at mRNA and protein levels and its serum levels were significantly higher in patients with HCC than in non-HCC subjects (P < 0.05). Altered expressions of various MMPs and growth signaling molecules, some of which were correlated with GPC3 expression, were observed in HCCs. Down-regulation of GPC3 expression by siRNA in GPC3-overexpressing HCC cell lines resulted in a significant decrease in expressions of MMP2, MMP14, fibroblast growth factor receptor 1, insulin-like growth factor 1 receptor. GPC3 expression was significantly correlated with nuclear/cytoplasmic localization of beta-catenin.
CONCLUSION: These results suggest that GPC3, in conjunction with MMPs and growth signaling molecules, might play an important role in the progression of HCC.