title: Crocidolite asbestos-induced signal pathway dysregulation in mesothelial cells.
abstract: BACKGROUND
  Malignant mesothelioma is a rare cancer caused by exposure to asbestos. Current therapies have limited efficacy and the prognosis is dismal. A better understanding of the underlying mechanism of asbestos-induced malignant transformation will help to identify molecular markers that can be used for diagnosis, prognosis or therapeutic targets.
  
  
  OBJECTIVE
  The objectives of this study are (1) to identify altered levels of proteins and phosphoproteins and (2) to establish the interactive network among those proteins in crocidolite-treated benign mesothelial cells and in malignant mesothelial cells.
  
  
  METHODS
  Total cellular proteins were extracted from benign mesothelial cells, crocidolite-treated mesothelial cells and malignant mesothelial cells. The expression levels of 112 proteins and phosphoproteins were analyzed using a multiplex immunoblot-based assay followed by computational analysis (Protein Pathway Array).
  
  
  RESULTS
  A total of 16 proteins/phosphoproteins (7 down-regulated and 9 up-regulated) were altered after exposure of benign mesothelial cells to crocidolite asbestos and the majority of them are involved in DNA damage repair and cell cycle regulation. In malignant mesothelial cells, 21 proteins/phosphoproteins (5 down-regulated and 16 up-regulated) were dysregulated and majority of them are involved in EGFR/ERK and PI3K/Akt pathways. Within the regulatory network affected by crocidolite, p53 and NF-κB complex are the most important regulators. There was substantial overlap in the regulatory networks between the asbestos-treated cells and malignant mesothelial cells.
  
  
  CONCLUSIONS
  Asbestos exposure has extensive effects on regulatory pathways and networks. These altered proteins may be used in the future to identify those with a high risk for developing malignant mesothelioma and as targets for preventing this deadly malignancy.
authors.affiliation: Shanghai Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Wang
authors.forename: Andrew
authors.initials: A
authors.lastname: Gillis
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhao
authors.forename: Eugene
authors.initials: E
authors.lastname: Lee
authors.forename: Josephine
authors.initials: J
authors.lastname: Wu
authors.forename: Fengchun
authors.initials: F
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.forename: David Y
authors.initials: DY
authors.lastname: Zhang
mesh_terms: D017638:Asbestos, Crocidolite / Q000494:pharmacology*; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008654:Mesothelioma / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D010750:Phosphoproteins; D011506:Proteins; D017638:Asbestos, Crocidolite