DETECTION OF A UNIQUE GAMMA-GLUTAMYL-TRANSPEPTIDASE MESSENGER-RNA SPECIES CLOSELY-RELATED TO THE DEVELOPMENT OF HEPATOCELLULAR-CARCINOMA INHUMANS - A NEW CANDIDATE FOR EARLY DIAGNOSIS OF HEPATOCELLULAR-CARCINOMA

Many studies concerning gamma-glutamyl transpeptidase (GGTP) in hepato cellular carcinoma (HCC) have suggested that changes in hepatic GGTP e xpression may be closely related to the development of HCC. However, i ts mechanisms are not well known, and genomic analysis of the specific GGTP to HCC is also lacking, Recently, the human GGTP complementary D NA (cDNA) sequences from fetal liver, placenta, and HepG2 cells have b een published. In the present study, we sought to clarify the distribu tion of the GGTP mesenger RNA (mRNA) molecular species in human liver and determine whether alterations in GGTP mRNA expression occur upon t he development of HCC, The specific primer sets for reverse-transcript ion polymerase chain reaction (PCR) corresponding to the 5'-noncoding human GGTP mRNA of fetal liver (type A), HepG2 cells (type B), and pla centa (type C) were prepared. Oligonucleotide probes specific for each type of mRNA were also synthesized. Liver tissues were obtained hom p atients with or without HCC, and total RNA was extracted. Total RNA wa s also extracted from various organs obtained from one male patient up on autopsy. Types of GGTP mRNAs were analyzed using type-specific prim er sets and oligonucleotide probes. The types of GGTP mRNA varied in d ifferent organs. In normal liver and diseased Liver without HCC, the m ain type of GGTP mRNA was type A. The expression was monogenic in most cases but was polygenic in some cases, In the polygenic cases, type C was common, but type B was found occasionally. On the other hand, typ e B was predominant in cancerous tissues with HCC. In noncancerous tis sues of livers with HCC, the main types were types A and B. The preval ence of type B was significantly higher in both cancerous and noncance rous tissues of livers with HCC than in livers without HCC. The preval ence of type A in cancerous tissue, but not in noncancerous tissue, wa s significantly lower than in livers without HCC. These results strong ly suggested that the GGTP mRNA expression in human liver may shift ho m type A to type B during the development of HCC. The high prevalence of type B in noncancerous tissues suggested that the shift of the GGTP mRNA may occur from the preneoplastic stage of hepatocytes.