Urocortin and corticotropin-releasing factor receptor 2 in human renal cell carcinoma: disruption of an endogenous inhibitor of angiogenesis and proliferation.
OBJECTIVE
Urocortin (Ucn) exerts its actions through activation of two corticotropin-releasing factor receptors (CRFRs), CRFR1 and CRFR2. Involvement of Ucn/CRFR2 system in pathophysiological conditions such as the regulation of angiogenesis and inhibition of proliferation has been already reported. Suppression of neovascularization through reduction of vascular endothelial growth factor and inhibition of tumor cell cycling is modulated mainly through activation of CRFR2. To find out a possible involvement of Ucn/CRFR2 in kidney tumor, we examined the expression of Ucn and CRFR2 in normal and tumoral kidney specimens.


METHODS
We applied reverse transcriptase PCR (n=14), immunofluorescence (IF) on tissue microarrays (n=25) and confocal microscopy to examine the mRNA expression and peptide/protein localization of Ucn and CRFR2 in normal kidney versus clear cell renal cell carcinoma, respectively.


RESULTS
Ucn and CRFR2 mRNAs are expressed in normal and tumor specimens. In normal tissue, IF showed a cytoplasmic staining of Ucn mainly in proximal tubules, whereas a diffuse nuclear staining with diverse intensity was observed in tumoral tissues. CRFR2 was detected in proximal tubules and vasculature of normal specimens. Intriguingly, an almost complete loss of CRFR2 was observed in epithelial cells and microvessels within tumor tissues.


CONCLUSIONS
Here, and for the first time, we show the expression of Ucn and CRFR2 in human kidney and renal cell carcinoma. We propose that the nuclear translocation of Ucn along with the loss of CRFR2 in epithelial cells and microvasculature of tumoral specimens may be involved in the pathobiology of renal cell carcinoma.
Department of Urology and Urological Oncology, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. tezval.hossein@mh-hannover.de
Hossein
H
Tezval
Stefanie
S
Jurk
Farahnaz
F
Atschekzei
Jan U
JU
Becker
Olaf
O
Jahn
Jürgen
J
Serth
Markus A
MA
Kuczyk
D000328:Adult; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D002455:Cell Division / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D004847:Epithelial Cells / Q000473:pathology / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000473:pathology / Q000502:physiology; D007680:Kidney Neoplasms / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D054832:Urocortins / Q000235:genetics* / Q000378:metabolism
C101531:CRF receptor type 2; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins