title: Biglycan is overexpressed in pancreatic cancer and induces G1-arrest in pancreatic cancer cell lines.
abstract: OBJECTIVE
  Biglycan (PG-I), a component of the extracellular matrix (ECM), is overexpressed in pancreatic cancer. To determine possible matrix-tumor interactions, we investigated the effects of PG-I on pancreatic cancer.
  
  
  METHODS
  PG-I expression in cell lines and tissue samples was examined by Northern blot and immunofluorescence. The effect of PG-I on proliferation was determined by measuring activity of Ras, ERK, Rb, [(3)H]-thymidine incorporation, and cell cycle analysis. Expression of cyclin A, B1, D1, E1, G1, PCNA, p21, and p27 was analyzed by Northern and Western blots.
  
  
  RESULTS
  PG-I was overexpressed in the ECM of pancreatic cancer samples compared with normal pancreas or chronic pancreatitis tissues. Addition of transforming growth factor (TGF)-beta induced PG-I expression in HFL and HFFF2 fibroblasts as well as in the pancreatic cancer cell line PANC-1. PG-I inhibited growth of both TGF-beta-responsive and TGF-beta-unresponsive pancreatic cancer cells by inducing G1-arrest, which is accompanied by an increase of p27 and reduction of cyclin A and proliferating cell nuclear antigen. Furthermore, endogenous Ras and ERK activation was partly reduced by PG-I in vitro.
  
  
  CONCLUSIONS
  The ECM protein PG-I inhibits growth by arresting pancreatic cancer cells in G1 and may be part of a host defense mechanism aimed at slowing down pancreatic tumor progression.
authors.affiliation: Department of Internal Medicine I, University of Ulm, Ulm, Germany.
authors.forename: C K
authors.initials: CK
authors.lastname: Weber
authors.forename: G
authors.initials: G
authors.lastname: Sommer
authors.forename: P
authors.initials: P
authors.lastname: Michl
authors.forename: H
authors.initials: H
authors.lastname: Fensterer
authors.forename: M
authors.initials: M
authors.lastname: Weimer
authors.forename: F
authors.initials: F
authors.lastname: Gansauge
authors.forename: G
authors.initials: G
authors.lastname: Leder
authors.forename: G
authors.initials: G
authors.lastname: Adler
authors.forename: T M
authors.initials: TM
authors.lastname: Gress
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D058578:Biglycan; D018797:Cell Cycle Proteins / Q000032:analysis / Q000378:metabolism; D019925:Cyclin A / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016326:Extracellular Matrix Proteins; D005260:Female; D016193:G1 Phase / Q000502:physiology*; D016195:G2 Phase / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011509:Proteoglycans / Q000032:analysis / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000032:analysis / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D016160:Retinoblastoma Protein / Q000032:analysis / Q000378:metabolism; D016196:S Phase / Q000502:physiology; D017154:Stromal Cells / Q000737:chemistry / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D025521:Tumor Suppressor Proteins
chemical_list: C546884:BGN protein, human; C546885:Bgn protein, mouse; D058578:Biglycan; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D019925:Cyclin A; D016326:Extracellular Matrix Proteins; D018809:Proliferating Cell Nuclear Antigen; D011509:Proteoglycans; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)