36 KB728 KB33 KB199220252011Janeš, DamjanJevnikar, ZalaKikelj, DanijelKos, JankoMirković, BojanaRojnik, MatijaZidar, Naceštevilka:4letnik:45str. 259-266, IIISSN:1318-2099COBISSID:3157361URN:URN:NBN:SI:doc-TD6SH3VCenAssociation of Radiology and OncologyRadiology and oncology (Ljubljana)katepsin Hmorfogenetični protein 4proteolitični encimirak (medicina)Cathepsin H indirectly regulates morphogenetic protein-4 (BMP-4) in various human cell lines|Background. Cathepsin H is a cysteine protease considered to play a major role in tumor progression, however, its precise function in tumorigenesis is unclear. Cathepsin H was recently proposed to be involved in processing of bone morphogenetic protein 4 (BMP-4) in mice. In order to clarify whether cathepsin H also regulates BMP-4 in humans, its impact on BMP-4 expression, processing and degradation was investigated in prostate cancer (PC-3), osteosarcoma (HOS) and pro-monocytic (U937) human cell lines. Materials and methods. BMP-4 expression was founded to be regulated by cathepsin H using PCR array technology and confirmed by real time PCR. Immunoassays including Western blot and confocal microscopy were used to evaluate the influence of cathepsin H on BMP-4 processing. Results. In contrast to HOS, the expression of BMP-4 mRNA in U937 and PC3 cells was significantly decreased by cathepsin H. The different regulation of BMP-4 synthesis could be associated with the absence of the mature 28 kDa cathepsin H form in HOS cells, where only the intermediate 30 kDa form was observed. No co-localization of BMP-4 and cathepsin H was observed in human cell lines and the multistep processing of BMP-4 was not altered in the presence of specific cathepsin H inhibitor. Isolated cathepsin H does not cleave mature recombinant BMP-4, neither with its amino- nor its endopeptidase activity. Conclusions. Our results exclude direct proteolytic processing of BMP-4 by cathepsin H, however, they provide support for its involvement in the regulation of BMP-4 expressionTEXTznanstveno časopisjejournalsSlovenian National E-content AggregatorNational and University Library of SloveniaDruštvo radiologije in onkologije