Metallothionein isoform 1 and 2 gene expression in the human prostate: Downregulation of MT-1X in advanced prostate cancer

BACKGROUND Studies have shown an association of metallothionein (MT) overexpression with tumor type and grade. However, a family of genes underlies the expression of these proteins. The goals of this study were to define the expression of MT genes and protein in normal human prostate and to provide evidence that the expression of the MT isoforms is altered in prostate cancer. METHODS Immunohistochemistry was used to localize MT protein, reverse transcription‐polymerase chain reaction (RT‐PCR) to determine the MT isoform‐specific mRNAs, and immunoblot analysis to determine MT protein levels. RESULTS The localization of MT in the prostate was further defined using the E9 antibody. Using normal prostate tissue dissected from glands removed for prostate cancer, it was demonstrated that MT protein expression in the normal prostate is supported by mRNA from the MT‐1A, MT‐1E, MT‐1X, and MT‐2A genes. No expression of the MT‐1X gene was demonstrated in cases of advanced prostate cancer. The expression of MT‐1 and MT‐2 isoform‐specific mRNA varied among three commonly utilized prostate cancer cell lines. CONCLUSIONS MT protein in the normal human prostate is supported by transcription of mRNA from the MT‐1A, MT‐1E, MT‐1X, and MT‐2A genes. Expression of MT‐1X mRNA is downregulated in advanced prostate cancer. Variable expression of MT mRNA in prostate cell lines provides evidence that MT gene expression may be altered among individual prostate cancers. Prostate 43:125–135, 2000. © 2000 Wiley‐Liss, Inc.