Renal cell carcinoma and normal kidney protein expression.
Renal cell carcinoma (RCC), a human kidney cancer from the proximal tubular epithelium, accounts for about 3% of adult malignancies. Molecular 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 have not yet provided a marker for early renal cell carcinoma diagnosis. Current diagnostic methods do not help to detect the tumor before advanced stages. We therefore used two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) to study normal and tumor kidney tissues in ten patients suffering from RCC. A human kidney protein map in the SWISS-2DPAGE database accessible through the ExPASy WWW Molecular Biology Server was established. Of 2789 separated polypeptides, 43 were identified by gel comparison, amino acid analysis, N-terminal sequencing, and/or immunodetection. The comparison between normal and tumor kidney tissues showed four polypeptides to be absent in RCC. One of them was identified as ubiquinol cytochrome c reductase (UQCR), whose locus has elsewhere been tentatively assigned to chromosome 19p12 or chromosome 22. A second polypeptide was identified as mitochondrial NADH-ubiquinone oxido-reductase 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 transcription or translation. It might indicate that mitochondrial disfunction plays a major role in RCC genesis or evolution.
Sarto
C
C
University Department of Clinical Pathology, Desio Hospital, Milan, Italy. sarto@desiolab.unimi.it
Marocchi
A
A
Sanchez
J C
JC
Giannone
D
D
Frutiger
S
S
Golaz
O
O
Wilkins
M R
MR
Doro
G
G
Cappellano
F
F
Hughes
G
G
Hochstrasser
D F
DF
Mocarelli
P
P
D000595:Amino Acid Sequence; D002292:Carcinoma, Renal Cell / Q000737:chemistry* / Q000473:pathology; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000737:chemistry* / Q000473:pathology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000032:analysis*; D010449:Peptide Mapping
D009363:Neoplasm Proteins