Carcinogenesis, Vol 18, 545-551, Copyright © 1997 by Oxford University Press
T Imai, T Masui, M Ichinose, H Nakanishi, T Yanai, T Masegi, M Muramatsu and M Tatematsu
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.
ARTICLES
Reduction of glutathione S-transferase P-form mRNA expression in remodeling nodules in rat liver revealed by in situ hybridization
Laboratory of Pathology, Aichi Cancer Research Institute, Nagoya, Japan.
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