RGD Reference Report - A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases. - Rat Genome Database

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A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases.

Authors: Yin, JJ  Mohammad, KS  Kakonen, SM  Harris, S  Wu-Wong, JR  Wessale, JL  Padley, RJ  Garrett, IR  Chirgwin, JM  Guise, TA 
Citation: Yin JJ, etal., Proc Natl Acad Sci U S A 2003 Sep 16;100(19):10954-9. Epub 2003 Aug 26.
RGD ID: 734914
Pubmed: PMID:12941866   (View Abstract at PubMed)
PMCID: PMC196909   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.1830978100   (Journal Full-text)

Osteoblastic bone metastases are common in prostate and breast cancer patients, but mechanisms by which tumor cells stimulate new bone formation are unclear. We identified three breast cancer cell lines that cause osteoblastic metastases in a mouse model and secrete endothelin-1. Tumor-produced endothelin-1 stimulates new bone formation in vitro and osteoblastic metastases in vivo via the endothelin A receptor. Treatment with an orally active endothelin A receptor antagonist dramatically decreased bone metastases and tumor burden in mice inoculated with ZR-75-1 cells. Tumor-produced endothelin-1 may have a major role in the establishment of osteoblastic bone metastases, and endothelin A receptor blockade represents effective treatment.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Neoplasm Metastasis  ISOEdn1 (Mus musculus)734914; 734914 RGD 
Neoplasm Metastasis  IDA 734914 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Edn1  (endothelin 1)

Genes (Mus musculus)
Edn1  (endothelin 1)

Genes (Homo sapiens)
EDN1  (endothelin 1)


Additional Information