Abstract
The L-pyruvate kinase (L-PK) gene is slightly active in normal and tumoral endocrine pancreatic tissues while, in vivo, this gene is not transcribed in the exocrine pancreas. Nevertheless, the L-PK gene is re-expressed at a very low level in cultured 266.6 cells derived from an exocrine pancreas carcinoma. The L-PK gene is early activated in endodermal tissues, e.g. yolk sac and primitive intestine; it remains transcribed in fetal pancreas. In adult, L-PK gene expression is restricted to some endocrine cells. Hepatocyte nuclear factor (HNF) 1 and HNF4 are the main tissue-restricted transcription factors involved in tissue-specific expression of the L-PK gene. HNF1 concentration is similar in liver and all pancreatic cells. HNF4 concentration is high in liver, much lower in islets of Langerhans, endocrine pancreatic tumors, and cultured insulinoma cells, and is scarcely detectable in adult exocrine pancreas. This distribution of HNF4 parallels the expression of the L-PK gene. In vivo footprinting experiments show that the HNF1 binding site is similarly occupied in both adult liver and adult pancreas, in which this gene is practically inactive. In this latter tissue, however, the HNF4 binding site is differently occupied with respect to the liver. Since the chromatin structure remains open around the L-PK promoter in pancreas, the L-PK gene can probably be re-expressed under certain circumstances, for instance in cancerous pancreatic cells.
Highlights
The L-pyruvate kinase (L-PK) igsesnleightly active in dietary dependent targeted oncogenesis was created in transnormal and tumoral endocrinepancreatic tissues while, genic mice by using asa transgene a DNA fragment encoding in uiuo,this gene is not transcribed in the exocrine pan- large T and little t SV40 antigens under the control of 3.2 creas
The L-PK gene is re-expressed at a kilobase pairs of regulatory sequences of the rat L-PK gene very low level in cultured 266.6 cells derived from an (L-PwTag).These sequences carried all information necessary exocrine pancreas carcinoma
Hepatocyte nuclear factor (HNF) 1 and HNF4 are the main tissue-restricted transcription factors involved in tissue-specific expression of the L-PK gene
Summary
The L-pyruvate kinase (L-PK) igsesnleightly active in dietary dependent targeted oncogenesis was created in transnormal and tumoral endocrinepancreatic tissues while, genic mice by using asa transgene a DNA fragment encoding in uiuo,this gene is not transcribed in the exocrine pan- large T and little t SV40 antigens under the control of 3.2 creas. In adult tissues,L-PK mRNA was detected after 25 cycles of PCR only in those already known to express the L-PK gene: liver (loo%), kidney (20%1),and intestine
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