Characterization of nuclear matrix protein alterations associated with renal cell carcinoma

Nuclear matrix proteins (NMPs), which constitute the nuclear skeleton, play a role in regulating gene expression and are thought to play an important role in carcinogenesis. Five NMPs specific to renal cell carcinoma (RCC) have been previously identified, RCCA 1 to 5. Our aim was to identify the sequence of these novel NMPs that are associated with RCC.

NMPs were extracted from five conventional clear cell RCC specimens from patients undergoing surgical excision for presumed RCC. The RCCA proteins identified were analyzed by matrix-assisted light desorption ionization mass spectrometry to determine their peptide mass fingerprint. This fingerprint was then analyzed by searching the Mascot and National Institutes of Health BLAST (basic local alignment search tool) databases to determine protein identification.

Only RCCA-1 and RCCA-2 were able to be consistently identified from each tumor specimen by the reverse staining method necessary to perform mass spectrometry. Mass spectrometry peptide mass fingerprinting revealed that RCCA-1 appears to be a differentially spliced form of nucleoporin p54 that has been identified in endometrial carcinoma. RCCA-2 was identified as an albumin-like protein.

This is the first report of nucleoporin p54 and albumin alterations in RCC. The identification of an abnormal nucleoporin in RCC suggests that alterations in nuclear transport might play a role in the development of this disease. The alterations in these NMPs suggest future areas for investigation in identifying diagnostic markers of, or therapeutic targets for, RCC.