%0 Journal Article
%T The ubiquitin-like molecule interferon-stimulated gene 15 (ISG15) is a potential prognostic marker in human breast cancer
%A Nuran Bektas
%A Erik Noetzel
%A Jščrgen Veeck
%A Michael F Press
%A Glen Kristiansen
%A Amjad Naami
%A Arndt Hartmann
%A Arno Dimmler
%A Matthias W Beckmann
%A Ruth Knščchel
%A Peter A Fasching
%A Edgar Dahl
%J Breast Cancer Research
%D 2008
%I BioMed Central
%R 10.1186/bcr2117
%X Using semiquantitative real-time PCR, cDNA dot-blot hybridisation and immunohistochemistry, we systematically analysed ISG15 expression in invasive breast carcinomas (n = 910) and normal breast tissues (n = 135). ISG15 protein expression was analysed in two independent cohorts on tissue microarrays; in an initial evaluation set of 179 breast carcinomas and 51 normal breast tissues; and in a second large validation set of 646 breast carcinomas and 10 normal breast tissues. In addition, a collection of benign and malignant mammary cell lines (n = 9) were investigated for ISG15 expression.ISG15 was overexpressed in breast carcinoma cells compared with normal breast tissue, both at the RNA and protein level. Recurrence-free (p = 0.030), event-free (p = 0.001) and overall (p = 0.001) survival analyses showed a significant correlation between ISG15 overexpression and unfavourable prognosis.Therefore, ISG15 may represent a novel breast tumour marker with prognostic significance and may be helpful in selecting patients for and predicting response to the treatment of human breast cancer.The interferon-stimulated gene 15 kDa (ISG15) is an interferon-inducible ubiquitin-like protein. In addition to being stimulated by type I interferon, expression of ISG15 is greatly induced by viral or bacterial infection through the Janus kinase/signal transducer and activator of transcription (Jak/STAT) signalling pathway [1-3]. After induction, ISG15 is secreted by monocytes, B- and T-lymphocytes and fibroblasts. The ISG15 protein is made up of tandem ubiquitin homology domains [4]. Within cells, ISG15 is covalently conjugated with cellular proteins in an enzymatic pathway (so called ISGylation) comprised of the activating E1, conjugating E2 and ligating E3 enzymes, which are similar to those used by ubiquitin (ubiquitylation). The conjugation of ISG15 with protein substrates provides a tag that either marks the labelled protein for degradation [5] or modulates its function [6]. Importantl
%U http://breast-cancer-research.com/content/10/4/R58