title: The ERK/MAPK pathway is overexpressed and activated in gallbladder cancer.
abstract: Gallbladder cancer (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. Molecular profiling has revealed that the deregulation in the ERK/MAPK signaling pathway plays a crucial role in many disease and malignancies, including GBC. The aim of this study was to measure the expression of ERK1/2 and p-ERK1/2 in a population with high GBC-related mortality, such as the Chilean population, and characterize the protein expression of this ERK/MAPK pathway in seven GBC cell lines. Immunohistochemistry (IHC) for ERK1/2 and p-ERK1/2 was performed in 123 GBC tissues and 37 chronic cholecystitis (CC) tissues. In addition, protein expression analysis by western blot for ERK1/2, p-ERK1/2, EGFR, ERBB2 and ERBB3 were performed in seven GBC cell lines (GB-d1, G415, NOZ, OCUG-1, TGBC-1, TGBC-2 and TGBC-24). A higher ERK1/2 and p-ERK1/2 expression was found in GBC tissues compared to chronic cholecystitis (CC) tissues (P<0.001). However, neither significant differences in overall survival nor significant associations with any of the clinicopathological features were found by comparing low and high expression of both ERK1/2 and p-ERK1/2. Western blot analysis of seven GBC cell lines showed that, in general, GB-d1, G415 and NOZ cells evidenced a strong expression of ERK1/2, p-ERK1/2, EGFR, ERBB2 and ERBB3. Therefore, ERK1/2 and p-ERK1/2 seem to be important in the development of GBC and GB-d1, G415 and NOZ cell lines may be used as experimental models for further in vitro and in vivo studies that help to decipher the role of MAPK/ERK pathway in gallbladder carcinogenesis.
authors.affiliation: Laboratory of Molecular Pathology, Department of Pathological Anatomy, School of Medicine, Universidad de La Frontera, Temuco, Chile; Center of Excellence in Translational Medicine - Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Universidad de La Frontera, Temuco, Chile.
authors.forename: Kurt
authors.initials: K
authors.lastname: Buchegger
authors.affiliation: Biomedicine Lab, School of Medicine, Universidad de La Frontera, Temuco, Chile; Center of Excellence in Translational Medicine - Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Universidad de La Frontera, Temuco, Chile.
authors.forename: Ramón
authors.initials: R
authors.lastname: Silva
authors.affiliation: Laboratory of Molecular Pathology, Department of Pathological Anatomy, School of Medicine, Universidad de La Frontera, Temuco, Chile; Center of Excellence in Translational Medicine - Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Universidad de La Frontera, Temuco, Chile.
authors.forename: Jaime
authors.initials: J
authors.lastname: López
authors.affiliation: Laboratory of Molecular Pathology, Department of Pathological Anatomy, School of Medicine, Universidad de La Frontera, Temuco, Chile; Center of Excellence in Translational Medicine - Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Universidad de La Frontera, Temuco, Chile.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ili
authors.affiliation: Department of Pathology, School of Medicine, Universidad de La Frontera, Temuco, Chile.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Araya
authors.affiliation: Biomedicine Lab, School of Medicine, Universidad de La Frontera, Temuco, Chile; Center of Excellence in Translational Medicine - Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Universidad de La Frontera, Temuco, Chile.
authors.forename: Pamela
authors.initials: P
authors.lastname: Leal
authors.affiliation: Laboratory of Molecular Pathology, Department of Pathological Anatomy, School of Medicine, Universidad de La Frontera, Temuco, Chile; Center of Excellence in Translational Medicine - Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Universidad de La Frontera, Temuco, Chile.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Brebi
authors.affiliation: Laboratory of Molecular Pathology, Department of Pathological Anatomy, School of Medicine, Universidad de La Frontera, Temuco, Chile; Center of Excellence in Translational Medicine - Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Universidad de La Frontera, Temuco, Chile. Electronic address: ismael.riquelme@ufrontera.cl.
authors.forename: Ismael
authors.initials: I
authors.lastname: Riquelme
authors.affiliation: Department of Pathology, UC Centre for Investigational Oncology (CITO), Advanced Centre for Chronic Diseases (ACCDiS), Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, Chile. Electronic address: jcroa@med.puc.cl.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Roa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D005260:Female; D005704:Gallbladder / Q000378:metabolism / Q000473:pathology; D005706:Gallbladder Neoplasms / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D015398:Signal Transduction; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: ERK/MAPK pathway; ERK1/2; Gallbladder cancer; Immunohistochemistry