Overexpression of human aspartyl(asparaginyl)beta-hydroxylase in hepatocellular carcinoma and cholangiocarcinoma.

Lavaissière, Laurent; Jia, Steve; Nishiyama, Mitsuru; Monte, Suzanne de la; Stern, Andrew M.; Wands, Jack R.; Friedman, Paul A.

doi:10.1172/jci118918

Cited by 140 publications

(234 citation statements)

References 42 publications

Supporting

Mentioning

225

Contrasting

Order By: Relevance

“…This suggests that in these transmembrane proteins, the extracellular domain regulates signal transduction by the cytoplasmic domain. 12,[24][25][26] In vivo and in vitro experiments have demonstrated that highlevel aspartyl beta-hydroxylase expression is linked to malignant transformation and invasive growth of malignant neoplasms. 27,28 It has been demonstrated that overexpression of the aspartyl beta-hydroxylase cDNAs in NIH-3T3 cells induces a transformed phenotype manifested by increased numbers of transformed foci, anchorage-independent growth, and tumorigenesis in nude mice.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies revealed that the aspartyl beta-hydroxylase is overexpressed in four of 10 hepatocellular carcinomas and a number of other malignant neoplasms, including those of gastrointestinal, mammary, bronchial, pancreatic, or biliary origin, but not in most normal adult tissues. [10][11][12]28 A research showed that aspartyl betahydroxylase has an important role in regulating invasive or metastatic tumor cell growth of human cholangiocarcinoma, and that high levels of aspartyl beta-hydroxylase expression correlate with poor prognosis. 11 Our results also showed that a significantly higher tumor aspartyl beta-hydroxylase protein expression level was associated with the presence of intrahepatic metastasis and the progression of histological grade.…”

Section: Discussionmentioning

confidence: 99%

“…It has been demonstrated previously that the aspartyl betahydroxylase gene is upregulated in human malignancies such as breast, colon, liver, and bile duct tumors. [10][11][12] But the role of aspartyl beta-hydroxylase in cell migration, oncogenesis, cell differentiation, invasiveness, properties, and cellular functions that propagate the malignant phenotype are not understood. In this study, aspartyl beta-hydroxylase expression was examined in hepatocellular carcinoma.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Expression of aspartyl beta-hydroxylase and its clinicopathological significance in hepatocellular carcinoma

et al. 2006

View full text Add to dashboard Cite

The human aspartyl beta-hydroxylase is a highly conserved enzyme that hydroxylates epidermal growth factorlike domains in transformation-associated proteins. The aspartyl beta-hydroxylase gene is upregulated in many human malignancies. The purpose of this study was to investigate the expression of aspartyl beta-hydroxylase in hepatocellular carcinoma. Aspartyl beta-hydroxylase mRNA levels were measured in 161 hepatocellular carcinomas and paired nontumoros liver tissues by conventional and real-time RT-PCR. Immunohistochemical staining of aspartyl beta-hydroxylase was performed using EnVision Plus system. The results showed that aspartyl beta-hydroxylase was overexpressed in 150 of 161 hepatocellular carcinomas (93%), including 45 of 48 unifocal small hepatocellular carcinomas (94%). Aspartyl beta-hydroxylase was highly expressed in hepatocellular carcinoma cells in contrast to its low level of expression in non-neoplastic liver cells. The protein expression level of aspartyl beta-hydroxylase in the hepatocellular carcinoma was parallel with the mRNA expression level (r ¼ 0.6594, Po0.0001). A significantly higher tumor aspartyl beta-hydroxylase overexpression level was associated with the presence of intrahepatic metastasis and the progression of histological grades. In conclusion, aspartyl beta-hydroxylase is overexpressed frequently in hepatocellular carcinoma, including early-stage small hepatocellular carcinoma, indicating that overexpression of aspartyl beta-hydroxylase plays a role in the development and progression of hepatocellular carcinoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Expression of aspartyl beta-hydroxylase and its clinicopathological significance in hepatocellular carcinoma

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Moreover, tissue inhibitors of MMP (Mohanam et al, 1995;Nakano et al, 1995) can modulate the integrity of extracellular matrix and tumor cell invasion. In this regard, the human aspartyl (asparaginyl) ␤-hydroxylase (AAH) gene is of interest because of its potential role in regulating infiltrative or metastatic growth of malignant neoplasms through ␤-hydroxylation of extracellular matrix molecules or receptors that contain the required epidermal growth factor-like domain consensus sequence (Ince et al, 1997(Ince et al, , 2000Lavaissiere et al, 1996).…”

mentioning

confidence: 99%

“…The human AAH cDNA encodes a 757-amino acid protein with a predicted M r of~86 kd (Lavaissiere et al, 1996). AAH is a member of the ␣-ketoglutarate-dependent dioxygenase family, which includes prolyl-3, prolyl-4, and lysyl hydroxylases (Jia et al, 1992;Wang et al, 1991).…”

mentioning

confidence: 99%

Role of the Aspartyl-Asparaginyl-β-Hydroxylase Gene in Neuroblastoma Cell Motility

Sepe

Lahousse

Gemelli

et al. 2002

Laboratory Investigation

View full text Add to dashboard Cite

SUMMARY:Aspartyl (asparaginyl) ␤-hydroxylase (AAH) is overexpressed in various malignant neoplasms, and high levels of immunoreactivity mainly occur in infiltrating or metastasized tumors. In addition, AAH is abundantly expressed in normally invasive placental trophoblastic cells. These observations led to the hypothesis that AAH may have a role in motility and aggressive behavior of tumor cells. The present study demonstrates that AAH is overexpressed in primary human malignant neuroectodermal tumors, including medulloblastomas and neuroblastomas, and that AAH expression is at a low level or undetectable in the normal mature brain. In the Sy5y neuroblastoma cell line, endogenous expression of the~86-kd AAH protein was demonstrated by Western blot analysis, and immunoreactivity predominantly localized to the cell surface by immunocytochemical staining and FACS analysis. Sy5y cells that were stably transfected with the human AAH cDNA had increased levels of proliferating cell nuclear antigen and Bcl-2, and reduced levels of p21/Waf1 and p16. In addition, increased AAH expression enhanced Sy5y cell motility, whereas antisense oligodeoxynucleotide inhibition of AAH significantly reduced Sy5y cell motility and increased the levels of p21/Waf1 and p16. The findings suggest that AAH overexpression contributes to the malignant phenotype of neuroectodermal tumor cells by increasing motility and enhancing proliferation, survival, and cell cycle progression. Because AAH expression is at a low level or undetectable in normal brain, the AAH gene may be a target for treating primitive neuroectodermal tumors. (Lab Invest 2002, 82:881-891).

show abstract

Biopharmaceuticals: Post‐Translational Modification Carboxylation and Hydroxylation

Brown

Stenberg

2009

Post‐translational Modification of Protein Biopharmaceuticals

View full text Add to dashboard Cite

Overexpression of human aspartyl(asparaginyl)beta-hydroxylase in hepatocellular carcinoma and cholangiocarcinoma.

Cited by 140 publications

References 42 publications

Expression of aspartyl beta-hydroxylase and its clinicopathological significance in hepatocellular carcinoma

Expression of aspartyl beta-hydroxylase and its clinicopathological significance in hepatocellular carcinoma

Role of the Aspartyl-Asparaginyl-β-Hydroxylase Gene in Neuroblastoma Cell Motility

Biopharmaceuticals: Post‐Translational Modification Carboxylation and Hydroxylation

Contact Info

Product

Resources

About