The peptide AM (adrenomedullin) is stimulated by hypoxia through HIF-1 (hypoxia-inducible factor-1). The majority of human CC-RCCs (clear cell renal cell carcinomas) display mutations in the tumour suppressor protein von Hippel–Lindau, which leads to constitutively elevated HIF-1. We hypothesized that AM is increased in CC-RCC tumours and that AM is a plasma biomarker for CC-RCC. Tumours and non-malignant kidney tissue were obtained from patients that underwent unilateral nephrectomy. Blood samples were drawn at the day of surgery, 3–6 days after surgery and 4–5 weeks after surgery. AM mRNA and peptide expression in tissue and AM plasma concentration were determined. HIF-1α was localized in tissue by immunohistochemistry. AM mRNA was elevated in CC-RCC compared with adjacent renal cortex (6-fold, n=18; P<0.02). There was no difference in AM mRNA between cortex and non-CC-RCC tissue (n=7). AM peptide concentration was elevated in CC-RCC tissue compared with adjacent cortex (4-fold, n=6; P<0.02), whereas there was no difference between cortex and non-CC-RCC tissue (n=5). HIF-1α immunoreactivity was detected in the majority of cell nuclei in 76% of CC-RCC, consistent with constitutive stabilization. In non-CC-RCC, HIF-1α staining was focal. Before surgery there was no difference in plasma AM concentration between tumour types. Nephrectomy increased plasma AM significantly after 3–6 days and a similar pre-surgery level was observed after 4–5 weeks in both groups of tumour patients. We conclude that elevated tissue AM is a distinguishing feature of CC-RCC compared with other kidney tumours. Plasma AM is not suited as a tumour marker for this disease.
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July 2006
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Research Article|
June 14 2006
Tissue expression and plasma levels of adrenomedullin in renal cancer patients
Jens Michelsen;
Jens Michelsen
*Department of Physiology and Pharmacology, University of Southern Denmark, DK-5000 Odense, Denmark
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Helle Thiesson;
Helle Thiesson
*Department of Physiology and Pharmacology, University of Southern Denmark, DK-5000 Odense, Denmark
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Steen Walter;
Steen Walter
†Department of Urology, Odense University Hospital, DK-5000 Odense, Denmark
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Peter D. Ottosen;
Peter D. Ottosen
‡Department of Pathology, Odense University Hospital, DK-5000 Odense, Denmark
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Ole Skøtt;
Ole Skøtt
*Department of Physiology and Pharmacology, University of Southern Denmark, DK-5000 Odense, Denmark
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Boye L. Jensen
*Department of Physiology and Pharmacology, University of Southern Denmark, DK-5000 Odense, Denmark
Correspondence: Dr Boye L. Jensen (email [email protected]).
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Publisher: Portland Press Ltd
Received:
February 06 2006
Revision Received:
March 02 2006
Accepted:
March 06 2006
Accepted Manuscript online:
March 06 2006
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2006
Clin Sci (Lond) (2006) 111 (1): 61–70.
Article history
Received:
February 06 2006
Revision Received:
March 02 2006
Accepted:
March 06 2006
Accepted Manuscript online:
March 06 2006
Citation
Jens Michelsen, Helle Thiesson, Steen Walter, Peter D. Ottosen, Ole Skøtt, Boye L. Jensen; Tissue expression and plasma levels of adrenomedullin in renal cancer patients. Clin Sci (Lond) 1 July 2006; 111 (1): 61–70. doi: https://doi.org/10.1042/CS20060030
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