Expression of oxidative phosphorylation genes in renal tumors and tumoral cell lines.
To investigate the regulation of genes encoding the proteins involved in energy metabolism in cancer cells, we studied the expression of several mitochondrial and nuclear genes involved in ATP production. Northern blot analysis was performed on renal tumors of different types: a clear cell carcinoma, an oncocytoma, and urothelial tumors at two different stages. The steady-state transcript patterns were compared with those observed in cell lines derived from renal tumors and in transformed cell lines. Striking differences were revealed among the three types of tumors, their respective controls, and the cultured renal cells. The levels of all mitochondrial transcripts were lower in tumor biopsies and tumoral cell lines than in the normal cell types. Moreover, a higher transcript level of nuclear genes involved in oxidative phosphorylation was observed in the oncocytomas and in the more malignant urothelial tumor. Different transcript patterns were observed in each of the tumoral and transformed cell lines, explaining the difference in metabolism between the different tumors and the tumoral or transformed cell lines. In particular, a high transcript level for the adenine nucleotide translocator isoform 2(ANT2) gene, which is usually not expressed in differentiated cells, was observed in oncocytoma and malignant urothelial renal tumor. This phenomenon was also observed in renal carcinoma cell lines and transformed cells. These data provide the first argument for the involvement of the ANT2 protein in glycolytic ATP uptake in cancer cell mitochondria and suggest a possible ANT2 antisense strategy for cancer therapy.
Faure Vigny
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H
Centre de Génétique Moléculaire et Cellulaire, UMR 5534 du CNRS-Université Claude Bernard Lyon I, Villeurbanne, France.
Heddi
A
A
Giraud
S
S
Chautard
D
D
Stepien
G
G
D015152:Blotting, Northern; D002292:Carcinoma, Renal Cell / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology / Q000235:genetics*; D000226:Mitochondrial ADP, ATP Translocases / Q000235:genetics; D010085:Oxidative Phosphorylation; D012334:RNA, Neoplasm / Q000235:genetics; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004272:DNA, Mitochondrial; D012334:RNA, Neoplasm; D000226:Mitochondrial ADP, ATP Translocases