In vivo gene expression profile analysis of metallothionein in renal cell carcinoma

The antiapoptotic and mitogenic responses of metallothionein (MT) have been well documented in vitro. While MT protein overexpression, frequently enco untered in a number of human primary tumors, has been shown to be correlate d with disease progression, little information is available on the in vivo isoform expression of MT. In this study we have demonstrated the occurrence of MT proteins and further defined their differential expression profile i n human primary renal cell carcinoma (RCC). Pooled normal human kidney RNA and paired biopsy specimens (tumor and control) obtained from 11 patients d iagnosed with RCC with tumor grade ranging from 1-3 and a pathological stag ing of T2-T3 (N0M0) were used for the study. Samples were analyzed for;he p resence of MT protein using immunohistochemical (IHC) analysis and for MT i soform-specific mRNA expression by reverse transcriptase polymerase chain r eaction. Metallothionein protein assumed both cytoplasmic and nuclear stain ing in cancer cells and was detected in eight of 11 samples (72%) with poly clonal antibodies. The immunoreactivity of MT protein, but not its cellular localization, in RCC specimens suggests a relationship between and advance d disease. While alterations in the basal level of expression of MT-1E, MT- 1F and MT-1X genes remained unchanged, significant up-regulation of MT-2A a nd clown-regulation of MT-1A and MT-1G transcripts was observed in RCC tiss ue specimens when compared with controls. Intriguingly, the paired RCC biop sy specimens had lower MT-1H transcripts than pooled normal human controls. We here provide the first report of the differential expression of MT isof orms in human RCC and that this data further support the role of MT-2A in t umorigenesis. (C) 2000 Elsevier Science ireland Ltd. All rights reserved.