Protein kinase D1 drives pancreatic acinar cell reprogramming and progression to intraepithelial neoplasia
Authors: Peter Storz
Richard Panayiotou
Geou-Yarh Liou
Ursula B Braun
Derek C Radisky
Howard C Crawford
Q Jane Wang
Heike Döppler
Nicole R Murray
Alan P Fields
Michele Scotti Buzhardt
Michael Leitges
Journal: Nature Communications (2015)
Discipline: Multidisciplinary
Keywords: transdifferentiation; pancreatic acinar cells; ductal phenotype; acinar-to-ductal metaplasia; ADM
Affiliations: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, Florida 32224, USA., The Biotechnology Centre of Oslo, University of Oslo, N-0349 Oslo, Norway., Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.

Abstract:  The transdifferentiation of pancreatic acinar cells to a ductal phenotype (acinar-to-ductal metaplasia, ADM) occurs after injury or inflammation of the pancreas and is a reversible process. However, in the presence of activating Kras mutations or persistent epidermal growth factor receptor (EGF-R) signalling, cells that underwent ADM can progress to pancreatic intraepithelial neoplasia (PanIN) and eventually pancreatic cancer. In transgenic animal models, ADM and PanINs are initiated by high-affinity ligands for EGF-R or activating Kras mutations, but the underlying signalling mechanisms are not well understood. Here, using a conditional knockout approach, we show that protein kinase D1 (PKD1) is sufficient to drive the reprogramming process to a ductal phenotype and progression to PanINs. Moreover, using 3D explant culture of primary pancreatic acinar cells, we show that PKD1 acts downstream of TGFα and Kras, to mediate formation of ductal structures through activation of the Notch pathway. 

Retracted: No

PubPeer comments:
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 Each paper was submitted while the other one was not published. Both focus on unrelated topics but use the PKD1 fl fl mice that were generated by Dr. Leitges. For publication (in Nature Communications) we felt we had to provide the scheme how the PKD1 floxed mice were generated in the Leitges laboratory in the Supplemental Data, because at that time this information was not published. In my communication with the editor at Nature Communications I pointed this out and got the OK to use this scheme as a Supplemental Figure. You can e-mail me directly at storz.peter@mayo.edu and I can forward you the communication with the editor. PS: Both figures look similar because they are based on the scheme how the PKD1 fl fl mice were made by the Leitges laboratory. , 
 #2 When you submit papers for publication it is standard practice for the editors to ask if you intend to publish something like it. The rule is that if something has already been published that it should be stated in the figure legend. Using the close proximity of publications dates ( because at that time this information was not published ) provides encouragement to others to submit the same data close together in time. How you considered asking for a correction to be made to the paper submitted second? A journal subverting standard practice does not reflect well on that journal. , 
 This is not the same data. It is not data at all. This only a scheme how the PKD1 floxed mice were made by Dr. Leitges. Including this figure was discussed with the editor and was of no concern at that time. Moreover, our paper was published first, and if, then this would need to be addressed by Dr. Leitges for his paper. I can not speak for him. ,