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Transfection of the Multiple Endocrine Neoplasia Type 1 Gene to a Human Endocrine Pancreatic Tumor Cell Line Inhibits Cell Growth and Affects Expression of JunD, δ-Like Protein 1/Preadipocyte Factor-1, Proliferating Cell Nuclear Antigen, and QM/Jif-1

Authors :
Peter Stålberg
Britt Skogseid
Gunnar Westin
Mårten Santesson
Daniel Lindberg
Jonas Rastad
Kjell Öberg
Yinghua Zhou
Per Grimfjärd
Anders Gobl
Shu Wang
Source :
The Journal of Clinical Endocrinology & Metabolism. 89:2326-2337
Publication Year :
2004
Publisher :
The Endocrine Society, 2004.

Abstract

In the absence of metastases or overgrowth to adjacent organs, the lack of reliable markers for malignancy is a well-recognized problem for clinicians managing patients with endocrine tumors. Apart from inactivation of the multiple endocrine neoplasia type 1 (MEN1) gene, the molecular mechanisms involved in tumorigenesis of the endocrine organs and MEN1-associated nonendocrine lesions are vastly unknown. To try to learn more about down-stream effects on MEN1 gene inactivation, we used the BON1 cells, showing low levels of endogenous menin, and transfected them with a MEN1 gene construct. On restoring the menin expression, we recorded inhibition of cell growth. We also performed macroarray and present data on differentially expressed genes in the transfected cells, after corroboration by Northern blots and quantitative PCR. JunD was up-regulated in menin-expressing clones, whereas delta-like protein 1/preadipocyte factor-1 (involved in differentiation and growth of the pancreatic endocrine cells), proliferating cell nuclear antigen, and QM/Jif-1 (a negative regulator of c-Jun) became down-regulated. These findings might contribute to the understanding of the tissue-specific features of MEN1. We also show that homozygous inactivation of the MEN1 gene statistically correlates to higher expression of delta-like protein 1/preadipocyte factor-1, proliferating cell nuclear antigen, and QM/Jif-1, as well as lower MEN1 expression, in a limited sample of malignant endocrine pancreatic tumors.

Details

ISSN :
19457197 and 0021972X
Volume :
89
Database :
OpenAIRE
Journal :
The Journal of Clinical Endocrinology & Metabolism
Accession number :
edsair.doi...........ef58fbbeccace6062669f28acd2b109d
Full Text :
https://doi.org/10.1210/jc.2003-031228