Pancreatic regenerating gene I and acinar cell differentiation: influence on cellular lineage.
OBJECTIVE
Pancreatic regenerating gene I (reg I) has been implicated in cellular differentiation. Acinar cells can transdifferentiate into other pancreatic-derived cells, and we postulated that changes in intracellular levels of reg I would affect the state of differentiation.


METHODS
We transfected AR42J cells with a plasmid containing the entire coding sequence of reg I and isolated clones with complementary DNA in sense (SS) or antisense (AS) orientation. Levels of messenger RNA (mRNA) and protein expression were examined by Western blotting and real-time polymerase chain reaction.


RESULTS
Expression of reg I was confirmed in SS or AS clones. AR42J transfected with SS demonstrated more acinarlike phenotype, whereas those transfected with AS showed a less differentiated state. Specifically, amylase mRNA and protein levels increased in SS cells, whereas AS cells showed increased pancreatic and duodenal homeobox 1 (Pdx1) and insulin mRNAs and cytokeratin protein. Conversely, cytokeratin and Pdx1 were depressed in SS cells.


CONCLUSIONS
These data demonstrate that in acinar cells, reg I overexpression is linked to acinar cell differentiation, whereas inhibition of reg I leads to beta cell and possibly ductal phenotype. Reg I expression in acinar cells is important in maintaining pancreatic cell lineage, and when decreased, cells can dedifferentiate and move toward becoming other pancreatic cells.
Sanchez
Didier
D
Department of Surgery, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA.
Mueller
Cathy M
CM
Zenilman
Michael E
ME
D000681:Amylases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D018267:Carcinoma, Acinar Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D019070:Cell Lineage; D049109:Cell Proliferation; D018076:DNA, Complementary / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D051847:Lithostathine / Q000235:genetics / Q000378:metabolism*; D008858:Microscopy, Phase-Contrast; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D018076:DNA, Complementary; D018398:Homeodomain Proteins; D007328:Insulin; D051847:Lithostathine; D012333:RNA, Messenger; C497616:Reg1a protein, rat; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D000681:Amylases