Tumor suppressor Pdcd4 is a major transcript that is upregulated during in vivo pancreatic islet neogenesis and is expressed in both beta-cell and ductal cell lines.
OBJECTIVE
We wished to identify a major transcript that is upregulated during in vivo pancreatic islet neogenesis and examine the expression of the gene in beta and ductal cells.


METHODS
Differential display polymerase chain reaction was used to identify upregulated transcripts after islet neogenesis was stimulated in the rat by brief occlusion of the main pancreatic duct. The expression of this major transcript, namely PDCD4 (programmed cell death gene 4), was measured in beta and ductal cells after stimulation with the incretin hormone glucagon-like peptide 1, mitogenic insulin, the thiazolidinedione rosiglitazone, and by high glucose concentrations. The subcellular location of the protein was also examined.


RESULTS
The expression of the Pdcd4 gene in pancreatic beta and ductal cells was found to be stimulated in a comparable manner by either glucagon-like peptide 1, insulin, and by high glucose concentrations. However, intracellular localisation of the PDCD4 protein was shown to be differentially regulated by these stimuli in beta and ductal cells. Furthermore, the thiazolidinedione rosiglitazone specifically upregulates Pdcd4 gene expression in beta cells in a time-dependent manner.


CONCLUSIONS
This is the first study showing Pdcd4 expression in pancreatic cells. Our data indicate that Pdcd4 expression may be integral in the function of the adult pancreas.
Ferris
William F
WF
Division of Endocrinology, Department of Medicine, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, South Africa. WFerris@sun.ac.za
Marriott
Claire E
CE
Ali
Tomader
T
Landy
Caroline
C
Campbell
Susan C
SC
Macfarlane
Wendy M
WM
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000502:physiology*; D010183:Pancreatic Ducts / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; D007328:Insulin; C467042:Pdcd4 protein, rat; D045162:Thiazolidinediones; D025521:Tumor Suppressor Proteins; D000077154:Rosiglitazone; D052216:Glucagon-Like Peptide 1