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Neurogenin 3 and neurogenic differentiation 1 are retained in the cytoplasm of multiple endocrine neoplasia type 1 islet and pancreatic endocrine tumor cells
Uppsala universitet, Institutionen för medicinska vetenskaper. (Endokrin tumörbiologi)
Uppsala universitet, Endokrinkirurgi.ORCID iD: 0000-0001-7366-6258
Uppsala universitet, Institutionen för medicinska vetenskaper. (Endokrin tumörbiologi)
Uppsala universitet, Endokrinkirurgi.
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2009 (English)In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 38, no 3, 259-266 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES:

To investigate if transcription factors involved in pancreatic differentiation and regeneration are present in pancreatic endocrine tumors and if they are differentially expressed in normal pancreas compared with multiple endocrine neoplasia type 1 (MEN1) nontumorous pancreas.

METHODS:

The expression of neurogenin 3 (NEUROG3), neurogenic differentiation 1 (NEUROD1), POU class 3 homeobox 4 (POU3F4), pancreatic duodenal homeobox factor 1 (PDX1), ribosomal protein L10 (RPL10), delta-like 1 homolog (Drosophila; DLK1), and menin was analyzed by immunohistochemistry in normal pancreas and pancreatic endocrine tumors from 6 patients with MEN1 and 16 patients with sporadic tumors, as well as pancreatic specimens from Men1 heterozygous and wild type mice. Quantitative polymerase chain reaction was performed in a subset of human tumors.

RESULTS:

Tumors and MEN1 nontumorous endocrine cells showed a prominent cytoplasmatic NEUROG3 and NEUROD1 expression. These factors were significantly more expressed in the cytoplasm of Men1 heterozygous mouse islet cells compared with wild type islets; the latter showed an exclusively nuclear reactivity. The degree of Pou3f4, Rpl10, and Dlk1 immunoreactivities differed significantly between islets of heterozygous and wild type mice. The expressions of RPL10 and NEUROD1 were prominent in the MEN1 human and heterozygous mouse exocrine pancreas. Insulinomas had significantly higher PDX1 and DLK1 messenger RNA levels compared with other tumor types.

CONCLUSIONS:

Transcription factors involved in pancreatic development show altered expression and subcellular localization in MEN1 nontumorous pancreas and pancreatic endocrine tumors.

Place, publisher, year, edition, pages
2009. Vol. 38, no 3, 259-266 p.
Keyword [en]
MEN1, pancreas, transcription factors, subcellular localization
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:rkh:diva-1478DOI: 10.1097/MPA.0b013e3181930818PubMedID: 19307926OAI: oai:DiVA.org:rkh-1478DiVA: diva2:794230
Available from: 2009-11-18 Created: 2015-03-10 Last updated: 2015-03-11Bibliographically approved

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