title: Identification of biomarkers associated with the development of hepatocellular carcinoma in CuZn superoxide dismutase deficient mice.
abstract: To identify biomarkers associated with the development of hepatocellular carcinoma (HCC) in CuZn superoxide dismutase (CuZnSOD, Sod1) deficient mice, 2-DE followed by MS analysis was carried out with liver samples obtained from 18-month-old Sod1-/- and +/+ mice. The intracellular Ca binding protein, regucalcin (RGN), showed a divergent alteration in Sod1-/- samples. Whereas elevated RGN levels were observed in -/- samples with no obvious neoplastic changes, marked reduction in RGN was observed in -/- samples with fully developed HCC. GST mu1 (GSTM1), on the other hand, showed a significant increase only in the neoplastic regions obtained from Sod1-/- livers. No change in GSTM1 was observed in the surrounding normal tissues. Marked reduction was observed in two intracellular lipid transporters, fatty acid binding protein 1 (FABP1) and major urinary protein 11 and 8 (MUP 11&8), in Sod1-/- samples. Analysis of additional samples at 18-22 months of age showed a three-fold increase in enolase activities in Sod1-/- livers. Consistent with previous findings, carbonic anhydrase 3 (CAIII) levels were significantly reduced in Sod1-/- samples, and immunohistochemical analysis revealed that the reduction was not homogenous throughout the lobular structure in the liver.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
authors.forename: Sailaja
authors.initials: S
authors.lastname: Elchuri
authors.forename: Mohammed
authors.initials: M
authors.lastname: Naeemuddin
authors.forename: Orr
authors.initials: O
authors.lastname: Sharpe
authors.forename: William H
authors.initials: WH
authors.lastname: Robinson
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Huang
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D024403:Carbonic Anhydrase III / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005982:Glutathione Transferase; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D020543:Proteome / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology*; D053719:Tandem Mass Spectrometry
chemical_list: D002135:Calcium-Binding Proteins; D024403:Carbonic Anhydrase III; D050556:Fatty Acid-Binding Proteins; D005982:Glutathione Transferase; D047908:Intracellular Signaling Peptides and Proteins; D010751:Phosphopyruvate Hydratase; D011506:Proteins; D020543:Proteome; D013482:Superoxide Dismutase; C493320:Fabp1 protein, mouse; C513324:Rgn protein, mouse; C035737:major urinary proteins