title: Downregulation of several fibulin genes in prostate cancer.
abstract: BACKGROUND
  Fibulins, encoded by FBLN genes, are extracellular matrix proteins influencing cell adhesion and migration. Altered expression of fibulins is associated with progression of several cancer types, but has not been studied in prostate cancer.
  
  
  METHODS
  Expression of FBLN1 (major splice forms C and D), FBLN4, FBLN5, SPOCK1, and TENC was compared between 47 prostate cancer samples and 13 benign prostatic tissues by quantitative RT-PCR. Fibulin-1 and fibulin-5 expression was studied by immunohistochemistry. Effects of androgens and the DNA methylation inhibitor 5-aza-2'-deoxycytidine on fibulin expression were investigated in different prostate cancer cell lines.
  
  
  RESULTS
  Our recent microarray analysis suggested downregulation of three fibulins, FBLN1, FBLN4, and FBLN5, in prostate cancer, while two further ECM genes, SPOCK1 (testican) and TENC (tenascin C), appeared upregulated or unchanged. These observations were corroborated by quantitative RT-PCR. Accordingly, FBLN1 and FBLN4 were weakly expressed in carcinoma lines compared to normal prostate epithelial cells (PrECs). Only FBLN4 was induced by 5-aza-2'-deoxycytidine, but its promoter was unmethylated. Androgen did not affect expression of FBLN genes. The FBLN1C and FBLN1D splice forms were coordinately expressed. Fibulin-1 protein was weakly detectable in benign PrECs, but tended to accumulate in cancer cells. Fibulin-5 was predominantly located in the stroma with a strong gradient from the periurethral to the peripheral zone, and lost in cancers.
  
  
  CONCLUSIONS
  Three FBLN genes are significantly downregulated in prostate cancer, whereas SPOCK1 is often upregulated. FBLN5 downregulation fits its postulated anticancerous function, whereas FBLN1 and FBLN4 behave different than in certain other cancers.
authors.affiliation: Department of Urology, Heinrich Heine University, Duesseldorf, Germany.
authors.forename: Agnes
authors.initials: A
authors.lastname: Wlazlinski
authors.forename: Rainer
authors.initials: R
authors.lastname: Engers
authors.forename: Michèle J
authors.initials: MJ
authors.lastname: Hoffmann
authors.forename: Christiane
authors.initials: C
authors.lastname: Hader
authors.forename: Volker
authors.initials: V
authors.lastname: Jung
authors.forename: Mirko
authors.initials: M
authors.lastname: Müller
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Schulz
mesh_terms: D000368:Aged; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D018628:Gene Dosage; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002135:Calcium-Binding Proteins; C403672:EFEMP2 protein, human; D016326:Extracellular Matrix Proteins; C492373:FBLN5 protein, human; D011509:Proteoglycans; D012333:RNA, Messenger; C504369:SPOCK1 protein, human; C060820:fibulin; D000077209:Decitabine; D001374:Azacitidine