title: Comparative proteomic analysis of two stress-management strategies in pancreatic cancer.
abstract: BACKGROUND
  It is known that cancers adopt different strategies to cope with stress and overcome adverse micro-environmental conditions. Such strategies are also applicable to chemo-therapeutic treatment, which could subsequently result in chemo-resistance.
  
  
  METHODS
  In order to investigate known stress-evasion strategies observed in pancreatic cancer, the stress-resistant KLM1-derived cell lines KLM1-R (Gemcitabine (GEM)-induced stress) and KLM1-S (growth factor restriction-induced stress) were employed. Comparative proteomics were employed between for the two cell lines that were also compared against the parent cell line KLM1.
  
  
  RESULTS
  Proteomic analysis revealed changes in the expression levels of 6 proteins, namely: transitional endoplasmic reticulum ATPase, lamin A/C, PDZ and LIM protein 1, calmodulin, heat shock protein 60 and alpha enolase. Resistance to GEM of KLM1-R and KLM1-S was found to be comparable, with KLM1-S cells exhibiting close to 1.5-fold higher half-maximal inhibitory concentration (IC50) compared to KLM1-R cells.
  
  
  CONCLUSIONS
  These results suggest that KLM1-R can be used as a model of directly-acquired chemoresistance (responding directly to evade GEM treatment), while KLM1-S is a good model of indirectly-acquired chemoresistance (formed in response to having to survive with less availability of growth factors), additionally gaining a selective advantage upon GEM treatment.
authors.affiliation: Department of Anatomy and Cell Biology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta Department of Biochemistry and Functional Proteomics, Graduate School of Medicine, Yamaguchi, Japan.
authors.forename: Byron
authors.initials: B
authors.lastname: Baron
authors.affiliation: Department of Biochemistry and Functional Proteomics, Graduate School of Medicine, Yamaguchi, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Fujioka
authors.affiliation: Department of Biochemistry and Functional Proteomics, Graduate School of Medicine, Yamaguchi, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Kitagawa
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushyu University, Fukuoka, Japan.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Maehara
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushyu University, Fukuoka, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.affiliation: Department of Biochemistry and Functional Proteomics, Graduate School of Medicine, Yamaguchi, Japan Centre of Clinical Laboratories in Tokuyama Medical Association Hospital, Shunan-shi, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Biochemistry and Functional Proteomics, Graduate School of Medicine, Yamaguchi, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kuramitsu
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D013058:Mass Spectrometry; D010190:Pancreatic Neoplasms / Q000473:pathology*; D040901:Proteomics; D013312:Stress, Physiological / Q000187:drug effects*; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Pancreatic cancer; proteomics; stress response; stress-induced