Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0030305 (
pancreatitis
)
16,014
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Pancreatic ductal adenocarcinoma (PDAC) is associated with metaplastic changes in the pancreas but the transcriptional program underlying these changes is incompletely understood. The zinc finger transcription factor,
PRDM3
, is lowly expressed in normal pancreatic acini and its expression increases during tumorigenesis. Although
PRDM3
promotes proliferation and migration of PDAC cell lines, the role of
PRDM3
during tumor initiation from pancreatic acinar cells in vivo is unclear. In this study, we showed that high levels of
PRDM3
expression in human pancreas was associated with
pancreatitis
, and well-differentiated but not poorly differentiated carcinoma. We examined
PRDM3
function in pancreatic acinar cells during tumor formation and
pancreatitis
by inactivating Prdm3 using a conditional allele (Ptf1a
CreER
;Prdm3
flox/flox
mice) in the context of oncogenic Kras expression and supraphysiological cerulein injections, respectively. In Prdm3-deficient mice, Kras
G12D
-driven preneoplastic lesions were more abundant and progressed to high-grade precancerous lesions more rapidly. This is consistent with our observations that low levels of
PRDM3
in human PDAC was correlated significantly with poorer survival in patient. Moreover, loss of Prdm3 in acinar cells elevated exocrine injury, enhanced immune cell activation and infiltration, and greatly increased acinar-to-ductal cell reprogramming upon cerulein-induced
pancreatitis
. Whole transcriptome analyses of Prdm3 knockout acini revealed that pathways involved in inflammatory response and Hif-1 signaling were significantly upregulated in Prdm3-depleted acinar cells. Taken together, our results suggest that Prdm3 favors the maintenance of acinar cell homeostasis through modulation of their response to inflammation and oncogenic Kras activation, and thus plays a previously unexpected suppressive role during PDAC initiation.
...
PMID:PRDM3 attenuates pancreatitis and pancreatic tumorigenesis by regulating inflammatory response. 3217 33
