Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Pathology

Supervisor

Dr. Rennian Wang

Abstract

Studies show that Menin, a tumour suppressor encoded by the multiple endocrine neoplasia type 1 (Men1) gene, is required during murine pancreatic development. In humans, mutation results in the MEN1 tumourigenic syndrome; however, knowledge of menin in human pancreatic development is limited. This study examined the expression pattern and functional role of menin during human fetal islet development. Immunostaining revealed the presence of nuclear menin within pancreatic cells from the 1st through 2nd trimester co-localizing with various developmental factors. Knockdown of MEN1 in human fetal islet-epithelial cells significantly increased apoptosis, reduced proliferation, and decreased SOX9, NKX2.2, and NKX6.1 mRNA levels (transcription factors required in maintenance of the progenitor pool and endocrine differentiation). Overexpression of MEN1 confirmed these results suggesting that menin promotes cell survival and proliferation, maintains the islet progenitor pool, and regulates islet differentiation in the human fetal pancreas: a different function compared to its anti-tumourigenic role during adulthood.

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