title: BGLAP is expressed in pancreatic cancer cells and increases their growth and invasion.
abstract: BACKGROUND
  Bone gamma-carboxyglutamate protein (BGLAP; osteocalcin) is a small, highly conserved molecule first identified in the mineralized matrix of bone. It has been implicated in the pathophysiology of various malignancies. In this study, we analyzed the expression and role of BGLAP in the normal human pancreas, chronic pancreatitis (CP), and pancreatic ductal adenocarcinoma (PDAC) using quantitative RT-PCR, immunohistochemistry, immunocytochemistry and enzyme immunoassays, as well as cell proliferation and invasion assays. Gene silencing was carried out using specific siRNA molecules.
  
  
  RESULTS
  Compared to the normal pancreas, BGLAP mRNA and protein levels were not significantly different in CP and PDAC tissues. BGLAP was faintly present in the cytoplasm of normal acinar cells but was strongly expressed in the cytoplasm and nuclei of tubular complexes and PanIN lesions of CP and PDAC tissues. Furthermore, BGLAP expression was found in the cancer cells in PDAC tissues as well as in 4 cultured pancreatic cancer cell lines. TNFalpha reduced BGLAP mRNA and protein expression levels in pancreatic cancer cell lines. In addition, BGLAP silencing led to reduction of both cell growth and invasion in those cells.
  
  
  CONCLUSIONS
  BGLAP is expressed in pancreatic cancer cells, where it potentially increases pancreatic cancer cell growth and invasion through autocrine and/or paracrine mechanisms.
authors.affiliation: Department of General Surgery, University of Heidelberg, Heidelberg, Germany. hany.kayed@med.uni-heidelberg.de
authors.forename: Hany
authors.initials: H
authors.lastname: Kayed
authors.forename: Sandor
authors.initials: S
authors.lastname: Bekasi
authors.forename: Shereen
authors.initials: S
authors.lastname: Keleg
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Michalski
authors.forename: Thomas
authors.initials: T
authors.lastname: Giese
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
authors.forename: Jörg
authors.initials: J
authors.lastname: Kleeff
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D020868:Gene Silencing; D006801:Humans; D007124:Immunoenzyme Techniques; D007797:Laminin / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D015675:Osteocalcin / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000235:genetics / Q000473:pathology; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D015675:Osteocalcin; C059485:matrigel; D003094:Collagen