Regulation of glutathione transferase P: a tumor marker of hepatocarcinogenesis.

Placental glutathione transferase (GST-P) is specifically expressed during rat haptocarcinogenesis, and has been used as a reliable tumor marker for experimental hepatocarcinogenesis in the rat. The regulation of this tumor marker gene may be associated with the process of carcinogeneisis. By elucidating the mechanisms of such tumor marker gene expression, we may shed light on the molecular mechanisms of carcinogenesis. We analyzed the regulation of the GST-P gene and found that the strong enhancer element GPE1 (GST-P enhancer-1) specifically regulates the GST-P gene by interacting with specific transcription factors in normal liver and during hepatocarcinogenesis. In particular, C/EBPalpha was required for the suppression of GST-P gene in normal liver, whereas the Nrf2/MafK heterodimer was required for the activation of this gene during hepatocarcinogenesis. In this Mini-Review, we describe the positive and negative regulatory mechanisms in the pre-cancerous and normal liver, respectively.