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Identification of biomarkers associated with the development of hepatocellular carcinoma in CuZn superoxide dismutase deficient mice
Author(s) -
Elchuri Sailaja,
Naeemuddin Mohammed,
Sharpe Orr,
Robinson William H.,
Huang TingTing
Publication year - 2007
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200601011
Subject(s) - sod1 , hepatocellular carcinoma , superoxide dismutase , dismutase , intracellular , biology , chemistry , pathology , medicine , endocrinology , biochemistry , cancer research , oxidative stress
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.