title: Gremlin is overexpressed in lung adenocarcinoma and increases cell growth and proliferation in normal lung cells.
abstract: BACKGROUND
  Gremlin, a member of the Dan family of BMP antagonists, is a glycosylated extracellular protein. Previously Gremlin has been shown to play a role in dorsal-ventral patterning, in tissue remodeling, and recently in angiogenesis. Evidence has previously been presented showing both over- and under-expression of Gremlin in different tumor tissues. Here, we sought to quantify expression of Gremlin in cancers of the lung and performed in vitro experiments to check whether Gremlin promotes cell growth and proliferation.
  
  
  RESULTS
  Expression of Gremlin in 161 matched tumor and normal lung cancer specimens is quantified by quantitative real-time PCR and protein level is measured by immunohistochemistry. GREM1 was transfected into lung fibroblast and epithelial cell lines to assess the impact of overexpression of Gremlin in vitro.
  
  
  RESULTS
  Lung adenocarcinoma but not squamous cell carcinoma shows a significant increase in Gremlin expression by mRNA and protein level. Lung fibroblast and epithelial cell lines transfected with GREM1 show significantly increased cell proliferation.
  
  
  CONCLUSIONS
  Our data suggest that Gremlin acts in an oncogenic manner in lung adenocarcinoma and could hold promise as a new diagnostic marker or potential therapeutic target in lung AD or general thoracic malignancies.
authors.affiliation: Thoracic Oncology Laboratory, Department of Surgery, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Mulvihill
authors.forename: Yong-Won
authors.initials: YW
authors.lastname: Kwon
authors.forename: Sharon
authors.initials: S
authors.lastname: Lee
authors.forename: Li Tai
authors.initials: LT
authors.lastname: Fang
authors.forename: Helen
authors.initials: H
authors.lastname: Choi
authors.forename: Roshni
authors.initials: R
authors.lastname: Ray
authors.forename: Hio Chung
authors.initials: HC
authors.lastname: Kang
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Mao
authors.forename: David
authors.initials: D
authors.lastname: Jablons
authors.forename: Il-Jin
authors.initials: IJ
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology
chemical_list: C486399:GREM1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm