NF-κB signal transduction is a potential therapeutic target in many malignant tumors.
We have recently shown, in malignant renal proximal tumor cells, that a transcription complex, consisting of NF-κB p65 and mitogen-activated protein kinase p38α, joined by protein kinase C (PKC) α, transmigrates into the nucleus. There, PKCα suppresses the nuclear release of primary microRNA (pri-miRNA) 15a. Induced by endothelin (ET)-1, a decrease in PKCα levels leads to increased miRNA 15a (miR-15A) expression. An identical system can be identified in renal carcinomas, in which, after nuclear transmigration, PKCα binds directly to pri-miRNA 15a in the nucleus. However, the pattern of PKC isoforms differs between malignant renal cell carcinoma (RCC) and benign oncocytoma. PKCα, a component of the transcription complex in tumors, is up-regulated in benign oncocytoma but down-regulated in RCC. Conversely, miRNA 15a is up-regulated in RCC and down-regulated in oncocytoma. A similar behavior is observed in chromophobe carcinoma, whereas differences are less pronounced in papillary RCC (type I): NF-κB target gene expression (ie, ET-1, ET-A and ET-B receptors, vascular cell adhesion molecule-1, IL-6, and fractalkine) is particularly high in malignant RCCs. Up-regulated miRNA 15a can be measured in urine from patients with RCC but is nearly undetectable in oncocytoma, other tumors, and urinary tract inflammation. Thus, the up-regulation of miRNA 15a may be an important marker to help identify malignant clear-cell RCCs in both biopsy and urine samples.
Written by:
von Brandenstein M, Pandarakalam JJ, Kroon L, Loeser H, Herden J, Braun G, Wendland K, Dienes HP, Engelmann U, Fries JW. Are you the author?
Institute of Pathology, University Hospital, Cologne, Germany.
Reference: Am J Pathol. 2012 May;180(5):1787-97.
doi: 10.1016/j.ajpath.2012.01.014
PubMed Abstract
PMID: 22429968
UroToday.com Investigative Urology Section
