Mechanism of PAP I gene induction during hepatocarcinogenesis: clinical implications

British Journal of Cancer
N J DusettiJ L Iovanna

Abstract

Pancreatitis-associated protein I (PAP I) is a secretory protein first described as an acute phase reactant during acute pancreatitis. Recently, induction of the PAP I gene was also described in liver during hepatocarcinogenesis. To investigate the molecular mechanisms of this induction, we used constructs carrying progressive deletions of the PAP I promoter fused to the CAT gene. We showed that the silencer conferring tissue specificity on the PAP I gene was inactive in hepatoma cells. Then, in an vitro transcription system, we compared the transcription capacity of nuclear extracts from normal liver and HepG2 cells on constructs containing the silencer. The results confirmed that a trans-acting factor interacting with the PAP I silencer was present in liver cells and absent from hepatoma cells. On the other hand, immunohistochemistry showed that PAP I was expressed in a limited number of transformed hepatocytes. It was concluded that expression of PAP I in hepatocarcinoma occurred through inactivation of its silencer element and was not concomitant in all malignant cells. On that basis, we assayed PAP I in serum from patients with chronic hepatitis, liver cirrhosis or hepatocarcinoma. PAP I levels were normal in chronic activ...Continue Reading

Citations

May 18, 1999·International Journal of Cancer. Journal International Du Cancer·H RechrecheJ L Iovanna
Nov 7, 2002·Physiological Genomics·Mary Beth GenterBruce J Aronow
Nov 7, 2019·Frontiers in Cell and Developmental Biology·Zijing ChenEmmanuel S Tzanakakis
Jul 4, 2002·Annals of the New York Academy of Sciences·M CervelloG Montalto
Jan 1, 1999·Addiction Biology·H Paajanen, I Nordback
Mar 29, 2002·The Journal of Laboratory and Clinical Medicine·Hideaki KazumoriYoshikazu Kinoshita
Mar 31, 1998·International Journal of Pancreatology : Official Journal of the International Association of Pancreatology·Y MotooN Sawabu

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