Downregulation of TNF receptor-associated protein-2/p97 in renal cell carcinoma.
Messenger RNA differential display was used to identify genes that are differentially expressed in normal kidney and kidney tumors. We isolated a clone that was uniquely expressed in the normal kidney cell line KCTL-22. The differential expression was confirmed by Northern blot analysis. The cloned cDNA showed 100% homology with type-1 TNF receptor-associated protein-2 (TRAP-2), which is identical to the 97-kDa subunit 2 of the 26S protease (p97). TRAP-2/p97 mRNA was absent or downregulated in two out of four renal cell carcinoma (RCC) lines and in one out of five tissue samples of freshly harvested RCC. All normal tissues tested showed TRAP-2/p97 expression, with highest expression being observed in heart and skeletal muscle. The TRAP-2/p97 mRNA was also detectable in tumor cell lines of nonrenal origin. However, expression levels varied considerably, low levels in particular being observed frequently in malignant melanoma. Although in the tested samples expression of additional subunits of the proteasome, like LMP-2, LMP-7, and LMP-10, were unaltered, the downregulation of TRAP-2/p97 in tumor tissue might affect the processing and presentation of tumor-associated antigens.
Stassar
M J
MJ
Department of Tumor Progression and Immune Defense, German Cancer Research Center, Heidelberg.
Pitzer
C
C
Zøller
M
M
D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D014407:Tumor Cells, Cultured
C109035:BTAF1 protein, human; D011506:Proteins; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID