Endothelin axis expression is markedly different in the two main subtypes of renal cell carcinoma

Douglas, Meaghan L., Richardson, Michelle M. and Nicol, David L. (2004) Endothelin axis expression is markedly different in the two main subtypes of renal cell carcinoma. Cancer, 100 10: 2118-2124. doi:10.1002/cncr.20222

Author Douglas, Meaghan L.
Richardson, Michelle M.
Nicol, David L.
Title Endothelin axis expression is markedly different in the two main subtypes of renal cell carcinoma
Journal name Cancer   Check publisher's open access policy
ISSN 0008-543X
Publication date 2004-01-01
Sub-type Article (original research)
DOI 10.1002/cncr.20222
Volume 100
Issue 10
Start page 2118
End page 2124
Total pages 7
Editor R. Pollack
Place of publication USA
Publisher John Wiley & Sons, Inc
Language eng
Subject C1
321015 Oncology and Carcinogenesis
730108 Cancer and related disorders
Abstract BACKGROUND. The endothelin axis has been implicated in cancer growth, angiogenesis, and metastasis, but to the authors' knowledge the expression of endothelin genes has not been defined in renal cell carcinoma (RCC). METHODS. Tissue specimens were harvested from both normal and tumor-affected regions at the time of radical nephrectomy from 35 patients with RCC (22 with clear cell RCC [ccRCC] and 13 with papillary RCC [PRCC]). Real-time reverse transcriptase-polymerase chain reaction analysis determined the expression profile of the preproendothelins (PPET-1, PPET-2, and PPET-3), the endothelin receptors (ETA and ETB), and the endothelin-converting enzymes (ECE-1 and ECE-2). RESULTS. PPET-1 was found to be up-regulated in ccRCC tumor specimens and down-regulated in PRCC tumor specimens. ETA was significantly down-regulated in PRCC tumor specimens. ECE-1 was expressed in all tissue specimens at comparable levels, with moderate but significant elevation in normal tissue specimens associated with PRCC. Of the other genes, PPET-2 and ETB were expressed in all tissue specimens and no differences were observed between tumor subtypes or tumor-affected and normal tissue specimens, whereas PPET-3 and ECE-2 were present in all tissue specimens but were barely detectable. CONCLUSIONS. The endothelin axis was expressed differently in the two main subtypes of RCC and appeared to match macroscopic features commonly observed in these tumors (i.e., high expression of PPET-I in hypervascular ccRCC contrasted against low PPET-1 and ETA expression in hypovascular PRCC). The presence of ECE-1 mRNA in these tissue specimens suggested that active endothelin ligands were present, indicating endothelin axis activity was elevated in ccRCC compared with normal kidney, but impaired in PRCC. The current study provided further evidence that it is not appropriate to consider ccRCC and PRCC indiscriminately in regard to treatment. (C) 2004 American Cancer Society.
Keyword Oncology
Endothelin Receptors
Endothelin-converting Enzyme
Real-time Polymerase Chain Reaction
Messenger-rna Expression
Receptor Activation
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2005 Higher Education Research Data Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 27 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 15 Aug 2007, 13:33:35 EST