PMID- 17188139 OWN - NLM STAT- MEDLINE DCOM- 20070130 LR - 20070716 IS - 0039-6060 (Print) IS - 0039-6060 (Linking) VI - 140 IP - 6 DP - 2006 Dec TI - Recognizing genes differentially regulated in vitro by the multiple endocrine neoplasia type 1 (MEN1) gene, using RNA interference and oligonucleotide microarrays. PG - 921-9; discussion 929-31 AB - 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 > or =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. FAU - Stalberg, Peter AU - Stalberg P AD - Department of Surgical Sciences, University Hospital, Uppsala, Sweden. FAU - Santesson, Marten AU - Santesson M FAU - Ekeblad, Sara AU - Ekeblad S FAU - Lejonklou, Margareta Halin AU - Lejonklou MH FAU - Skogseid, Britt AU - Skogseid B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061101 PL - United States TA - Surgery JT - Surgery JID - 0417347 RN - 0 (DNA, Neoplasm) RN - 0 (MEN1 protein, human) RN - 0 (NF-kappa B) RN - 0 (Proto-Oncogene Proteins) RN - 0 (RNA, Messenger) RN - 0 (RNA, Neoplasm) RN - 0 (Receptors, Notch) RN - 0 (Wnt Proteins) SB - IM CIN - Surgery. 2007 Jun;141(6):830-1. PMID: 17560264 MH - Cell Line, Tumor MH - DNA, Neoplasm/genetics MH - Gene Expression Profiling MH - Gene Expression Regulation, Neoplastic/*physiology MH - Genes, Neoplasm/*genetics/physiology MH - Humans MH - NF-kappa B/genetics/metabolism MH - *Oligonucleotide Array Sequence Analysis MH - Pancreatic Neoplasms/genetics/metabolism/pathology MH - Proto-Oncogene Proteins/*genetics/metabolism MH - *RNA Interference MH - RNA, Messenger/genetics/metabolism MH - RNA, Neoplasm/genetics MH - Receptors, Notch/genetics/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Transfection MH - Wnt Proteins/genetics/metabolism EDAT- 2006/12/26 09:00 MHDA- 2007/01/31 09:00 CRDT- 2006/12/26 09:00 PHST- 2006/03/25 00:00 [received] PHST- 2006/06/30 00:00 [accepted] PHST- 2006/12/26 09:00 [pubmed] PHST- 2007/01/31 09:00 [medline] PHST- 2006/12/26 09:00 [entrez] AID - S0039-6060(06)00494-6 [pii] AID - 10.1016/j.surg.2006.06.038 [doi] PST - ppublish SO - Surgery. 2006 Dec;140(6):921-9; discussion 929-31. doi: 10.1016/j.surg.2006.06.038. Epub 2006 Nov 1.