RENAL-CELL CARCINOMA AND NORMAL KIDNEY PROTEIN EXPRESSION

Renal cell carcinoma (RCC), a human kidney cancer from the proximal tu bular epithelium, accounts for about 3% of adult malignancies. Molecul ar and cytogenetic analysis have highlighted deletions, translocations , or loss of heterozygosity in the 3p21-p26, a putative RCC locus, as well as in 6q, 8p, 9pq, and 14pq. Studies on phenotypic expression of human kidney tissue and on post-translational modifications in RCC hav e not yet provided a marker for early renal cell carcinoma diagnosis. Current dignostic methods do not help to detect the tumor before advan ced stages. We therefore used two-dimensional polyacrylamide gel elect rophoresis (2-D PAGE) to study normal and tumor kidney tissues in ten patients suffering from RCC. A human kidney protein map in the SWISS-2 DPAGE database accessible through the ExPASy WWW Molecular Biology Ser ver was established. Of 2789 separated polypeptides, 43 were identifie d by gel comparison, amino acid analysis, N-terminal sequencing, and/o r immunodetection. The comparison between normal and tumor kidney tiss ues showed four polypeptides to be absent in RCC. One of them was iden tified as ubiquinol cytochrome c reductase (UQCR), whose locus has els ewhere been tentatively assigned to chromosome 19p12 or chromosome 22. A second polypeptide was identified as mitochondrial NADH-ubiquinone oxidoreductase complex I whose locus is located on chromosome 18p11.2 and chromosome 19q13.3. These result suggest that the lack of UQCR and of mitochondrial NADH-ubiquinone oxidoreductase complex I expression in RCC may be caused by unknown deletions, or by changes in gene trans cription or translation. It might indicate that mitochondrial disfunct ion plays a major role in RCC genesis or evolution.