Modified expression of plasma glutathione peroxidase and manganese superoxide dismutase in human renal cell carcinoma

Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) is a powerful tool to separate thousands of polypeptides and to highlight the modificati on of protein expression in malignant diseases. By applying 2-D PAGE to ten normal human kidney and ten homologous renal cell carcinoma (RCC) tissues, we found two peptides in all ten normal tissues but not in RCCs and, conve rsely, two peptides were detected in all RCCs but not in normal tissues. Us ing matrix-assisted laser desorption/ionization time-of-flight mass spectro metry (MALDI-TOF-MS) and internal sequence analysis, the two first peptides were identified as two isoforms of plasma glutathione peroxidase (GPxP). T he two other peptides isolated in all RCCs but not in normal tissues were i dentified by N-terminal sequence analysis as multimeric forms of manganese superoxide dismutase (Mn-SOD). No multimeric Mn-SODs and only two monomeric forms were detected in normal tissues. GPxP and Mn-SOD are metallo-enzymes encoded on chromosome 5q32 and on chromosome 6p25, respectively. Their reg ions are within the locus 5q21 --> qter and 6q21-6q27 on which deletions an d translocations are described in some cytogenetic studies of RCC transform ation. Therefore, our results might suggest a correlation between the modif ied expression of GPxP and Mn-SOD in tumor tissues and chromosomal modifica tions, and that the two proteins may be putative markers for diagnosis of R CC.*