Pancreatic differentiation 2 (PD2), a PAF (
RNA Polymerase II Associated Factor) complex subunit, is overexpressed in
pancreatic cancer cells and has demonstrated potential oncogenic property. Here, we report that PD2/Paf1 expression was restricted to acinar cells in the normal murine pancreas, but its expression increased in the ductal cells of KrasG12D/Pdx1Cre (KC) mouse model of
pancreatic cancer with increasing age, showing highest expression in neoplastic ductal cells of 50 weeks old mice. PD2/Paf1 was specifically expressed in
amylase and CK19 double positive metaplastic ducts, representing intermediate structures during pancreatic acinar-to-ductal
metaplasia (ADM). Similar PD2/Paf1 expression was observed in murine pancreas that exhibited ADM-like histology upon
cerulein challenge. In normal mice,
cerulein-mediated
inflammation induced a decrease in PD2/Paf1 expression, which was later restored upon recovery of the pancreatic parenchyma. In KC mice, however, PD2/Paf1
mRNA level continued to decrease with progressive dysplasia and subsequent neoplastic transformation. Additionally, knockdown of PD2/Paf1 in pancreatic acinar cells resulted in the abrogation of
Amylase,
Elastase and
Lipase (acinar marker)
mRNA levels with simultaneous increase in CK19 and CAII (ductal marker) transcripts. In conclusion, our studies indicate loss of PD2/Paf1 expression during acinar transdifferentiation in
pancreatic cancer initiation and PD2/Paf1 mediated regulation of lineage specific markers.