Association of gankyrin protein expression with early clinical stages and insulin-like growth factor-binding protein 5 expression in human hepatocellular carcinoma.

Abstract

UNLABELLED:

Gankyrin (also known as PSMD10) is a liver oncoprotein that interacts with multiple proteins including MDM2 and accelerates degradation of the tumor suppressors p53 and Rb. We produced a monoclonal anti-gankyrin antibody and immunohistochemically assessed the clinicopathological significance of gankyrin overexpression in 43 specimens of human hepatocellular carcinoma (HCC). Specific cytoplasmic staining for gankyrin was observed in 62.8% (27/43) of HCCs, which was significantly associated with low TNM stage (P = 0.004), no capsular invasion (P = 0.018), no portal venous invasion (P = 0.008), and no intrahepatic metastasis (P = 0.012). The cumulative survival rate of patients with gankyrin-positive HCC was significantly higher than that with gankyrin-negative HCC (P = 0.037). p53 and MDM2 were positively stained by antibodies in 30.2% and 23.3%, respectively, of HCCs, but neither was inversely associated with gankyrin expression. In the Huh-7 human HCC cell line, overexpression of gankyrin up-regulated expression of insulin-like growth factor binding protein 5 (IGFBP-5), whereas suppression of gankyrin expression by siRNA down-regulated it. Supression of IGFBP-5 expression inhibited proliferation of Huh-7 cells as well as U-2 OS osteosarcoma cells. In HCC specimens, positive staining for IGFBP-5 was observed by immunohistochemistry in 41.9% (18/43), and the level of expression was significantly correlated with that of gankyrin (rho = 0.629, P < 0.001).

CONCLUSION:

These results suggest that gankyrin plays an oncogenic role(s) mainly at the early stages of human hepatocarcinogenesis, and that IGFBP-5 inducible by gankyrin overexpression may be involved in it.

• Authors: Atsushi Umemura, Yoshito Itoh, Katsuhiko Itoh, Kanji Yamaguchi, Tomoki Nakajima, Hiroaki Higashitsuji, Hitoshi Onoue, Manabu Fukumoto, Takeshi Okanoue, Jun Fujita
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 47 Issue 2 Pg. 493-502 (Feb 2008) ISSN: 1527-3350 [Electronic] United States
• PMID: 18161051 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin-Like Growth Factor Binding Protein 5
• PSMD10 protein, human
• Proto-Oncogene Proteins
• Proteasome Endopeptidase Complex

Topics

• Animals
• Bone Neoplasms
• Carcinoma, Hepatocellular (pathology)
• Cell Line, Tumor
• Humans
• Insulin-Like Growth Factor Binding Protein 5 (genetics)
• Liver Neoplasms (pathology)
• Lymph Nodes (pathology)
• Mice
• Multiple Myeloma (genetics, pathology)
• Neoplasm Staging
• Osteosarcoma
• Plasmids
• Proteasome Endopeptidase Complex (genetics)
• Proto-Oncogene Proteins (genetics)
• Transfection