title: ITIH5, a novel member of the inter-alpha-trypsin inhibitor heavy chain family is downregulated in breast cancer.
abstract: 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 of ITIH5 expression in breast tumors by real-time PCR and RNA in situ hybridization. While normal breast epithelial cells clearly express ITIH5, expression is consistantly lost or strongly downregulated in invasive ductal carcinoma. ITIH5 mRNA was neither detectable in cancerous nor benign breast cell lines. We propose that loss of ITIH5 expression may be involved in breast cancer development.
authors.affiliation: metaGen Pharmaceuticals GmbH, Oudenarder Str. 16, 13347 Berlin, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Himmelfarb
authors.forename: Eva
authors.initials: E
authors.lastname: Klopocki
authors.forename: Susanne
authors.initials: S
authors.lastname: Grube
authors.forename: Eike
authors.initials: E
authors.lastname: Staub
authors.forename: Irina
authors.initials: I
authors.lastname: Klaman
authors.forename: Bernd
authors.initials: B
authors.lastname: Hinzmann
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.forename: André
authors.initials: A
authors.lastname: Rosenthal
authors.forename: Matthias
authors.initials: M
authors.lastname: Dürst
authors.forename: Edgar
authors.initials: E
authors.lastname: Dahl
mesh_terms: D000595:Amino Acid Sequence; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D044584:Carcinoma, Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D016373:DNA, Antisense / Q000494:pharmacology; D018450:Disease Progression; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010802:Phylogeny; D053491:Proteinase Inhibitory Proteins, Secretory; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D002352:Carrier Proteins; D016373:DNA, Antisense; C482680:ITIH5 protein, human; D053491:Proteinase Inhibitory Proteins, Secretory; D012333:RNA, Messenger