title: Dishevelled family proteins are expressed in non-small cell lung cancer and function differentially on tumor progression.
abstract: BACKGROUND
  Dishevelled (Dvl) family proteins are cytoplasmic mediators of the Wnt/beta-catenin signaling pathway and have recently been linked to cancers. However, the roles of individual Dvls and their expression in human cancers are poorly defined. This work aimed to characterize the expression of Dvls and their correlation to clinicopathological factors and beta-catenin expression in non-small cell lung cancer (NSCLC).
  
  
  METHODS
  We used immunohistochemistry to assess the presence of the three Dvl family proteins in 113 individual NSCLC specimens. Thirty-nine of the 113 cases were examined further for Dvl and beta-catenin protein expression in matched primary growths and autologous nodal metastases. We also examined the effect of Dvl-1 and Dvl-3 overexpression on beta-catenin expression and the invasive ability of A549 and QG56 lung cancer cells.
  
  
  RESULTS
  The positive expression rate in primary tumors was 53.1% (60/113) for total Dvl, 36.3% (41/113) for Dvl-1, 36.3% (41/113) for Dvl-2 and 41.6% (47/113) for Dvl-3, while normal adult bronchial and alveolar epithelia showed negative expression of all these proteins. The expression levels of all three Dvl proteins were significantly higher in adenocarcinomas than in squamous carcinomas, and were associated with poor tumor differentiation. The positive expression of Dvl-1 and Dvl-2 proteins was correlated to advanced pTNM stages (III-IV vs. I-II). In addition, the expression levels of Dvl-1 and Dvl-3 were significantly higher in nodal metastases than in primary growths, with the Dvl-1 expression correlating to beta-catenin expression in the metastases. Exogenous expression of Dvl-1 and Dvl-3 both enhanced the invasive ability of A549 and QG56 cells, but had differential effects on beta-catenin protein expression in either cell line, without influencing beta-catenin mRNA levels.
  
  
  CONCLUSIONS
  Expression of Dvl family proteins, Dvl-1, Dvl-2 and Dvl-3, is common in NSCLCs. They may contribute to the progression of NSCLCs, but Dvl-1 and Dvl-3 may function on this process through different signaling pathways.
authors.affiliation: Department of Pathology, China Medical University, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wei
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Yang
authors.forename: Qian-Ze
authors.initials: QZ
authors.lastname: Dong
authors.forename: Xin-Jun
authors.initials: XJ
authors.lastname: Dong
authors.forename: Yang
authors.initials: Y
authors.lastname: Han
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.forename: En-Hua
authors.initials: EH
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002465:Cell Movement; D018450:Disease Progression; D000072261:Dishevelled Proteins; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051176:beta Catenin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000606578:DVL1 protein, human; C000606581:DVL2 protein, human; C000606584:DVL3 protein, human; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D051176:beta Catenin