title: Latent transforming growth factor binding protein 4 (LTBP4) is downregulated in mouse and human DCIS and mammary carcinomas.
abstract: BACKGROUND
  Transforming growth factor beta (TGF-ß) is able to inhibit the proliferation of epithelial cells and is involved in the carcinogenesis of mammary tumors. Three latent transforming growth factor-ß binding proteins (LTBPs) are known to modulate TGF-ß functions.
  
  
  METHODS
  The current study analyses the expression profiles of LTBP4, its isoforms LTBP1 and LTBP3, and TGF-ß1, TGF-ß2, TGF-ß3, and SMAD2, SMAD3 and SMAD4 in human and murine (WAP-TNP8) DCIS compared to invasive mammary tumors. Additionally mammary malignant (MCF7, Hs578T, MDA-MB361) and non malignant cell lines (Hs578BsT) were analysed. Microarray, q-PCR, immunoblot, immunohistochemistry and immunofluorescence were used.
  
  
  RESULTS
  In comparison to non-malignant tissues (n = 5), LTBP4 was downregulated in all human and mouse DCIS (n = 9) and invasive mammary adenocarcinomas (n = 5) that were investigated. We also found decreased expression of bone morphogenic protein 4 (BMP4) and increased expression of its inhibitor gremlin (GREM1). Treatment of the mammary tumor cell line (Hs578T) with recombinant TGF-ß1 rescued BMP4 and GREM1 expression.
  
  
  CONCLUSIONS
  We conclude that the lack of LTBP4-mediated targeting in malignant mammary tumor tissues may lead to a possible modification of TGF-ß1 and BMP bioavailability and function.
authors.affiliation: Charité Berlin, CVK, Med. Klinik Hepatologie & Gastroenterologie, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Celine
authors.initials: C
authors.lastname: Kretschmer
authors.forename: Anne
authors.initials: A
authors.lastname: Conradi
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kemmner
authors.forename: Anja
authors.initials: A
authors.lastname: Sterner-Kock
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D016207:Cytokines; D015536:Down-Regulation / Q000235:genetics*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D053779:Latent TGF-beta Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism
chemical_list: D055415:Bone Morphogenetic Protein 4; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D051785:Smad Proteins; C113178:Grem1 protein, mouse; C486399:GREM1 protein, human; C509040:LTBP4 protein, human