title: Proteome characterization of a human urothelial cell line resistant to the bladder carcinogen 4-aminobiphenyl.
abstract: BACKGROUND
  The aromatic amine 4-aminobiphenyl (4-ABP) is an environmental and occupational contaminant known to be a major etiological agent of human bladder cancer. 4-ABP metabolites are able to form DNA adducts that may induce mutations and initiate bladder carcinogenesis. Cells exposed to 4-ABP may develop resistance to the carcinogen. The aim of the present study was to detect and identify proteins whose expression is altered in the bladder carcinoma RT112 sub-lines selected for acquired resistance to 4-ABP, in order to disentangle the mechanisms.
  
  
  RESULTS
  Differential proteome analysis of cell lysates showed an overall perturbation in cell metabolism and energy pathways in the 4-ABP-resistant human urothelial clones, with over-expression of membrane trafficking proteins such as annexin 2. The resistant clones had altered expression of many proteins linked directly (i.e. lamin A/C, programmed cell death 6 interacting protein) or indirectly (i.e. 94 kDa glucose-regulated protein, fatty acid-binding protein) to decreased apoptosis, suggesting that resistance to 4-ABP might be associated with low apoptotic activity.
  
  
  CONCLUSIONS
  Our data provide evidence that deregulation of apoptosis and membrane trafficking proteins might be strongly implicated in the selection of carcinogen resistant cells. Some of these proteins might have potential as biomarkers of resistance and cancer risk.
authors.affiliation: Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy. rpastorelli@marionegri.it
authors.forename: Roberta
authors.initials: R
authors.lastname: Pastorelli
authors.forename: Federica
authors.initials: F
authors.lastname: Saletta
authors.forename: Donatella
authors.initials: D
authors.lastname: Carpi
authors.forename: Roberta
authors.initials: R
authors.lastname: Campagna
authors.forename: Carlo
authors.initials: C
authors.lastname: dell'Osta
authors.forename: Silvia
authors.initials: S
authors.lastname: Schiarea
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: Luisa
authors.initials: L
authors.lastname: Airoldi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matullo