RGD Reference Report - Dimethylarginine dimethylaminohydrolase I enhances tumour growth and angiogenesis. - Rat Genome Database

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Dimethylarginine dimethylaminohydrolase I enhances tumour growth and angiogenesis.

Authors: Kostourou, V  Robinson, SP  Cartwright, JE  Whitley, GS 
Citation: Kostourou V, etal., Br J Cancer 2002 Sep 9;87(6):673-80.
RGD ID: 727432
Pubmed: PMID:12237779   (View Abstract at PubMed)
PMCID: PMC2364234   (View Article at PubMed Central)
DOI: DOI:10.1038/sj.bjc.6600518   (Journal Full-text)

Angiogenesis is a prerequisite for tumour progression and is highly regulated by growth factors and cytokines a number of which also stimulate the production of nitric oxide. Asymmetric dimethylarginine is an endogenous inhibitor of nitric oxide synthesis. Asymmetric dimethylarginine is metabolised by dimethylarginine dimethylaminohydrolase. To study the effect of dimethylarginine dimethylaminohydrolase on tumour growth and vascular development, the rat C6 glioma cell line was manipulated to overexpress the rat gene for dimethylarginine dimethylaminohydrolase I. Enhanced expression of dimethylarginine dimethylaminohydrolase I increased nitric oxide synthesis (as indicated by a two-fold increase in the production of cGMP), expression and secretion of vascular endothelial cell growth factor, and induced angiogenesis in vitro. Tumours derived from these cells grew more rapidly in vivo than cells with normal dimethylarginine dimethylaminohydrolase I expression. Immunohistochemical and magnetic resonance imaging measurements were consistent with increased tumour vascular development. Furthermore, dimethylarginine dimethylaminohydrolase activity was detected in a series of human tumours. This data demonstrates that dimethylarginine dimethylaminohydrolase plays a pivotal role in tumour growth and the development of the tumour vasculature by regulating the concentration of nitric oxide and altering vascular endothelial cell growth factor production.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of angiogenesis  IMP 727432 RGD 
positive regulation of nitric oxide biosynthetic process  IMP 727432 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dimethylargininase activity  IDA 727432 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ddah1  (dimethylarginine dimethylaminohydrolase 1)


Additional Information