title: BCAR1 protein plays important roles in carcinogenesis and predicts poor prognosis in non-small-cell lung cancer.
abstract: OBJECTIVE
  Our previous study suggested the potential clinical implications of BCAR1 in non-small-cell lung cancer (NSCLC) (Mol Diagn Ther. 2011. 15(1): 31-40). Herein, we aim to evaluate the predictive power of BCAR1 as a marker for poor prognosis in NSCLC cases, verify the carcinogenic roles of BCAR1 in the A549 lung adenocarcinoma cell line, and testify to the BCAR1/phospho-p38 axis.
  
  
  METHODS
  Between January 2006 and June 2010, there were a total of 182 patients with NSCLC (151 cases with available follow up data, and 31 cases lost to follow-up due to the invalid contact information). We inspected BCAR1, phospho-BCAR1(Tyr410), phospho-p38(Thr180/Tyr182) and p38 expression in NSCLC tissues and matched adjacent normal tissues by immunoblotting and IHC. After BCAR1 -RNA interference in A549 cells, we inspected the protein expression (BCAR1, phospho-BCAR1, phospho-p38 and p38) and performed cell biology experiments (cell growth, migration and cycle).
  
  
  RESULTS
  BCAR1 was overexpressed in NSCLC tissues (177/182) and cell lines (A549 and Calu-3). However, it was not detected in the normal adjacent tissue in 161 of the 182 cases. Higher BCAR1 levels were strongly associated with more poorly differentiated NSCLC and predicted poorer prognosis. BCAR1 knockdown caused cell growth arrest, cell migration inhibition and cell cycle arrest of A549 cells. Overexpression of BCAR1 was associated with activation of p38 in NSCLC cases, and BCAR1 knockdown caused reduction of phospho-p38 levels in A549 cells.
  
  
  CONCLUSIONS
  Overexpression of BCAR1 is a predictor of poor prognosis in NSCLC and plays important carcinogenic roles in carcinogenesis, probably via activation of p38 MAPK. However, further investigations are required immediately.
authors.affiliation: Thoracic Surgery Department, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Bo
authors.initials: B
authors.lastname: Deng
authors.forename: Ru-Wen
authors.initials: RW
authors.lastname: Wang
authors.forename: Qun-You
authors.initials: QY
authors.lastname: Tan
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.forename: Yao-Guang
authors.initials: YG
authors.lastname: Jiang
authors.forename: Jing-Hai
authors.initials: JH
authors.lastname: Zhou
mesh_terms: D000368:Aged; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D059447:Cell Cycle Checkpoints; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D050719:Crk-Associated Substrate Protein / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010766:Phosphorylation; D011379:Prognosis; D012044:Regression Analysis; D016019:Survival Analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C493841:BCAR1 protein, human; D050719:Crk-Associated Substrate Protein; D048051:p38 Mitogen-Activated Protein Kinases