Overexpression of human aspartyl (asparaginyl) beta-hydroxylase is associated with malignant transformation

Nedim Ince; Suzanne M de la Monte; Jack R Wands

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Overexpression of human aspartyl (asparaginyl) beta-hydroxylase is associated with malignant transformation

Journal article

Peer reviewed

Overexpression of human aspartyl (asparaginyl) beta-hydroxylase is associated with malignant transformation

Nedim Ince, Suzanne M de la Monte and Jack R Wands

Cancer research (Chicago, Ill.), Vol.60(5), pp.1261-1266

03/01/2000

PMID: 10728685

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Abstract

The human aspartyl (asparaginyl) beta-hydroxylase (HAAH) is a highly conserved enzyme that hydroxylates epidermal growth factor-like domains in transformation-associated proteins. We previously reported overexpression of the HAAH gene in human hepatocellular carcinomas and cholangiocarcinomas (L. Lavaissiere et al., J. Clin. Investig., 98: 1313-1323, 1996). In the present study, we determined whether HAAH protein overexpression was linked to cellular proliferation or malignant transformation of bile ducts by using a human disease and rat model of bile duct proliferation. In addition, the transforming properties of the AAH genes were assessed by transient and stable transfection of NIH-3T3 cells with human and murine wild-type as well as mutant cDNA constructs that lacked hydroxylation activity. Cellular characteristics of the malignant phenotype were assessed by formation of transformed foci, growth in soft agar, and tumor development in nude mice. We found that HAAH gene expression was undetectable during bile duct proliferation in both human disease and rat models as compared with cholangiocarcinoma. Overexpression of HAAH in NIH-3T3 cells was associated with generation of a malignant phenotype, and enzymatic activity was required for cellular transformation. These findings suggest that overexpression of HAAH is linked to cellular transformation of biliary epithelial cells.

Gene Expression Regulation, Enzymologic

Mixed Function Oxygenases - biosynthesis

Animals

Cell Transformation, Neoplastic - genetics

Humans

Gene Expression Regulation, Neoplastic

Rats

Mice

Mixed Function Oxygenases - genetics

Bile Ducts - enzymology

3T3 Cells

Bile Ducts - pathology

Details

Title: Subtitle: Overexpression of human aspartyl (asparaginyl) beta-hydroxylase is associated with malignant transformation
Creators: Nedim Ince - Massachusetts General Hospital Cancer Center, Department of Medicine, Harvard Medical School, Charlestown 02129, USA
Suzanne M de la Monte
Jack R Wands
Resource Type: Journal article
Publication Details: Cancer research (Chicago, Ill.), Vol.60(5), pp.1261-1266
PMID: 10728685
NLM abbreviation: Cancer Res
ISSN: 0008-5472
eISSN: 1538-7445
Grant note: CA-35711 / NCI NIH HHS AA-02666 / NIAAA NIH HHS
Language: English
Date published: 03/01/2000
Academic Unit: Gastroenterology and Hepatology; Internal Medicine
Record Identifier: 9984094729702771

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