EXPRESSION OF THE RAT GAMMA-GLUTAMYL-TRANSPEPTIDASE GENE FROM A SPECIFIC PROMOTER IN THE SMALL-INTESTINE AND IN HEPATOMA-CELLS

In the small intestine and in HTC hepatoma eels, the gamma-glutamyl tr anspeptidase (GGT) single-copy gene is transcribed into a 2.5 kb and a 2.2 kb mRNA. Cloning of the GGT cDNA sequences from HTC eels demonstr ates that the 2.5 kb mRNA (mRNA(IV-1)) differs from the other rat GGT transcripts by a 371-base unique leader sequence which maps in the gen e as 2 separate exons upstream of the 3 promoters which have been prev iously characterized. We established that the transcription of these t wo mRNAs is initiated on a new promoter (promoter IV) and occurs in th e small intestine, in the epididymis, and in some hepatoma cells. The primary transcript initiated on GGT promoter IV is then alternatively spliced into the 2.5 kb mRNA(IV-1) or the 2.2 kb mRNA(IV-2) which is s horter in its 5'-untranslated sequence. The rat GGT gene exhibits a co mplex transcriptional organization leading to the transcription of fiv e mRNAs from four independent promoters in a tissue-specific manner. T he expression of the GGT promoter IV in the HTC hepatoma cells as well as in the small intestine could reveal that the HTC-transformed cells originate from liver precursor cells which still have the capacity to evolve toward different lineages. Thus, the GGT promoter IV will be v aluable to isolate factors involved in the differentiation and carcino genic processes.