ITIH5, a novel member of the inter-[alpha]-trypsin inhibitor heavy chain family is downregulated in breast cancer

• Published in: Cancer letters Vol. 204; no. 1; p. 69
• Main Authors: Himmelfarb, Marina, Klopocki, Eva, Grube, Susanne, Staub, Eike, Klaman, Irina, Hinzmann, Bernd, Kristiansen, Glen, Rosenthal, André, Dürst, Matthias, Dahl, Edgar
• Format: Journal Article
• Language: English
• Published: Clare Elsevier Limited 10.02.2004
• Subjects: Breast cancer; Cloning; Genes; Hybridization; Lung cancer; Phylogenetics; Proteins; Rodents; Tumorigenesis; Tumors; Germany
• DOI: 10.1016/j.canlet.2003.09.011
• ISSN: 0304-3835

The inter-[alpha]-trypsin inhibitor (ITI) family constitutes a group of proteins built up from one light chain and a variable set of heavy chains. Originally identified as plasma protease inhibitors, recent data indicate that ITI plays a role in extracellular matrix (ECM) stabilization and in prevention of tumor metastasis. Here we describe cloning as well as phylogenetic and expression analysis of a novel member of the heavy chain gene family,ITIH5. ITIH5 contains the two domains conserved in all known ITIHs, the vault protein inter-alpha-trypsin (VIT) domain and a von Willebrand type A (vWA) domain. However, ITIH5 diverged early from a common ancestor of the other subfamilies. We found strong downregulation ofITIH5expression in breast tumors by real-time PCR and RNA in situ hybridization. While normal breast epithelial cells clearly expressITIH5, expression is consistantly lost or strongly downregulated in invasive ductal carcinoma.ITIH5mRNA was neither detectable in cancerous nor benign breast cell lines. We propose that loss ofITIH5expression may be involved in breast cancer development.