Reduction of glutathione S-transferase P-form mRNA expression in remodeling nodules in rat liver revealed by in situ hybridization.
Glutathione S-transferase P-form (GST-P) mRNA levels and distribution were sequentially analyzed by in situ hybridization histochemistry (ISH) in rat livers during and after induction of preneoplastic foci and nodules in the Solt-Farber model. Dot blot analysis showed GST-P transcripts in the liver to be elevated coincidental with the development of GST-P-positive lesions. GST-P ISH indicated that the majority of early foci and some of the resultant lesions showed uniformly high levels of GST-P mRNA. However, the majority of foci and nodules after completion of the selection regimen exhibited a progressive loss of staining for GST-P mRNA. Similar results were obtained for gamma-glutamyltransferase (GGT) transcripts, indicating that phenotypic reversion is controlled by factors operating at the level of gene expression in both cases. Expression of GST-P mRNA was high in all hepatocellular carcinoma samples, whereas the levels of GGT transcripts varied considerably, so that the two enzymes showed a degree of independence in their regulation. The present data for transcription suggest that GST-P is a stable marker of preneoplastic and neoplastic cells, not only at the protein but also at the mRNA level, throughout hepatocarcinogenesis in the rat. The reason why transcription of GST-P mRNA is switched off as part of the reversion to a normal organization remains to be elucidated.
Imai
T
T
Laboratory of Pathology, Aichi Cancer Research Institute, Nagoya, Japan.
Masui
T
T
Ichinose
M
M
Nakanishi
H
H
Yanai
T
T
Masegi
T
T
Muramatsu
M
M
Tatematsu
M
M
D015073:2-Acetylaminofluorene; D000818:Animals; D015415:Biomarkers; D002273:Carcinogens; D056486:Chemical and Drug Induced Liver Injury; D003043:Cocarcinogenesis; D004052:Diethylnitrosamine; D004790:Enzyme Induction; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000235:genetics; D006498:Hepatectomy / Q000009:adverse effects; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008107:Liver Diseases / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D008115:Liver Regeneration / Q000235:genetics*; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011916:Rats, Inbred F344; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis
D015415:Biomarkers; D002273:Carcinogens; D007527:Isoenzymes; D012333:RNA, Messenger; D004052:Diethylnitrosamine; D015073:2-Acetylaminofluorene; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase