Cloning and Expression of the Rat p8 cDNA, a New Gene Activated in Pancreas during the Acute Phase of Pancreatitis, Pancreatic Development, and Regeneration, and Which Promotes Cellular Growth

Abstract

To characterize at the molecular level the pancreatic emergency program set up by the pancreatic cells in response to pancreatitis, we have developed a strategy in which the phenotype of the pancreatitis affected pancreas is established by characterization of a large number of its transcripts. Herein, we describe the cloning, sequence, and expression of a new gene, named p8, which is strongly activated in pancreatic acinar cells during the acute phase of pancreatitis, in developing pancreas and during pancreatic regeneration. In acinar cells, p8 mRNA is expressed rapidly and specifically in response to cellular pancreatitis-induced injury; its induction occurred almost similarly in edematous and necrohemorrhagic pancreatitis, indicating that p8 mRNA is maximally activated even in response to a mild pancreatic injury. Furthermore, in vitro studies suggest that p8 mRNA is induced in pancreatic and non-pancreatic cells in response to some apoptotic stimuli. p8 acts as a promoter of cellular growth factor when its cDNA is transfected into COS-7 and AR4-2J cells. Although we failed to identify p8-related sequences, analysis of its primary and secondary structure suggests that p8 is a basic helix-turn-helix-containing gene with slight homology to several homeotic genes and sufficient signal to be targeted to the nucleus. We therefore propose p8 as a putative transcriptional factor which can regulate pancreatic growth.