title: Activation of AXL and antitumor effects of a monoclonal antibody to AXL in lung adenocarcinoma.
abstract: OBJECTIVE
  AXL (anexelekto) has been explored as a potential novel therapeutic target for non-small cell lung carcinoma (NSCLC) but its activation status has not been evaluated in NSCLC.
  
  
  METHODS
  We first immunolocalized the phosphorylated form of AXL in 112 lung adenocarcinoma cases and subsequently evaluated the anti-neoplastic effects of monoclonal antibody AXL in two lung adenocarcinoma cell lines, PC9 and A549.
  
  
  RESULTS
  Phospho-AXL immunoreactivity was detected in 59.8% of adenocarcinoma cases examined and tended correlate significantly with larger tumor size (p=0.08) and with overall survival of the patients (p=0.041). Results of in vitro analysis revealed that the monoclonal antibody to AXL significantly inhibited cell proliferation of PC9 and A549, lung adenocarcinoma cell lines, which was caused by an inhibition of extracellular signal-regulated kinase (ERK) activation.
  
  
  CONCLUSIONS
  AXL-targeted therapy, possibly through inhibiting ERK activation of carcinoma cells, could confer clinical benefits on patients with lung adenocarcinoma.
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan. hsasano@patholo2.med.tohoku.ac.jp.
authors.forename: Shinya
authors.initials: S
authors.lastname: Iida
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miki
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kazushige
authors.initials: K
authors.lastname: Mori
authors.forename: Mikiyoshi
authors.initials: M
authors.lastname: Saito
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Niikawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Hisafumi
authors.initials: H
authors.lastname: Yamada-Okabe
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D047368:Tumor Burden; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human
keywords: AXL; lung adenocarcinoma; monoclonal antibody therapy