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Recognizing genes differentially regulated in vitro by the multiple endocrine neoplasia type 1 (MEN1) gene, using RNA interference and oligonucleotide microarrays
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Endokrin tumörbiologi)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Endokrin tumörbiologi)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Endokrin tumörbiologi)
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2006 (English)In: Surgery, ISSN 0039-6060, E-ISSN 1532-7361, Vol. 140, no 6, 921-931 p.Article in journal (Refereed) Published
Abstract [en]

Background:

Data on downstream effects of MEN1 gene inactivation is scarce. In an effort to identify genes regulated by MEN1, we designed a silencing experiment in a human endocrine pancreatic tumor cell line (BON1).

Methods:

By using RNA interference, MEN1 mRNA expression was knocked-down by >85%. Gene expression was assessed by oligonucleotide microarrays and compared to expression in nonsilenced controls. We also investigated if genes were differentially expressed in 6 malignant endocrine pancreatic tumors (EPTs) with homozygous MEN1 inactivation compared to 2 without MEN1 gene alterations.

Results:

Using a cut-off of ≥2 times, 66 genes were found to be upregulated, and 22 were downregulated in the MEN1-silenced clones. We corroborated the microarray findings by performing quantitative-PCR on the RNA from the silencing experiments for 7 of the 88 differentially regulated genes. Genes involved in endocrine cell fate determination, as well as genes known to be involved in NFkappaB, Notch, and Wnt signaling pathways, were among genes verified as differentially regulated in vitro.

Conclusions:

The demonstration of pathways affected by silencing of MEN1 in vitro provides novel insight into neoplastic processes of potential importance in vivo, which warrants further study.

Place, publisher, year, edition, pages
2006. Vol. 140, no 6, 921-931 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-22744DOI: 10.1016/j.surg.2006.06.038ISI: 000243335800020PubMedID: 17188139OAI: oai:DiVA.org:uu-22744DiVA: diva2:50517
Available from: 2007-01-22 Created: 2007-01-22 Last updated: 2017-12-07Bibliographically approved

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Stålberg, PeterSantesson, MårtenEkeblad, SaraLejonklou, Margareta HalinSkogseid, Britt

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