Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2007) 14 OC4.5

ECE2007 Oral Communications Neuroendocriology basis (7 abstracts)

Lack of nuclear Hes1 expression coincides with transformation of endocrine pancreatic cells in Men1 knock out mice

Térèse Johansson , Margareta Halin Lejonklou & Britt Skogseid


Institution of Medical Sciences, Uppsala, Sweden.

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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