ISSN 1470-3947 (print)
ISSN 1479-6848 (online)

Searchable abstracts of presentations at key conferences in endocrinology

Published by BioScientifica
Endocrine Abstracts (2007) 14 OC4.5 
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Lack of nuclear Hes1 expression coincides with transformation of endocrine pancreatic cells in Men1 knock out mice

Térèse Johansson, Margareta Halin Lejonklou & Britt Skogseid

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Background: Homozygous inactivation of the MEN1 tumor suppressor gene frequently occurs in endocrine pancreatic tumors (EPT); however, a heterozygous germ line inactivation of the gene seems to lead to development of an increase amount of endocrine pancreatic cells. The Notch signaling cascade plays a vital role in sustaining the balance between cell proliferation, differentiation and apoptosis during pancreatic development. Whether Notch signaling is MEN1 dependent is unknown.

Aim: To explore the Notch pathway by means of the transcription factors Hes1, Hey1 and Mash1 expression pattern and their role in endocrine tumour progression by in Men1+/− mice.

Methods: Notch1, Hes1, Hey1, Mash1, and Men1 mRNA expression were investigated by qPCR. Fifteen mice (10 Men1+/−, five Wt, 12 or 18 month,) were used; the endocrine tissue was divided according to size: small islets, islets, small tumors and larger tumors. Protein expression were assessed by immunohistochemistry (13 Men1+/− and 12 Wt, 9–22 month)

Results: Men1, Notch1, Hes1, and Hey1 mRNA expression was found in endocrine tissue of all sizes; Mash1 was found in 28/55 samples. Variable degree of loss of menin (the Men1 protein) expression was observed in tumors of Men1+/− mice age 14–22 month. Men1+/− and Wt mice showed no difference in Notch1, Hey1, and Mash1 immunoreactivity. Wild type mice of all ages expressed nuclear Hes1, whereas only the younger Men1+/− mice displayed nuclear Hes1 immunoreactivity. The tumors of the heterozygous mice age 14–22 month had lost nuclear Hes1 expression.

Conclusions: Mash1 immunoreactivity was invariably and abundantly displayed. The lack of Hes1 in tumor cell nuclei in elderly Men1+/− mice indicates that Hes1 might be of importance in endocrine pancreatic tumorigenesis.

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