PMID- 22193451
OWN - NLM
STAT- MEDLINE
DCOM- 20130221
LR  - 20111223
IS  - 0371-0874 (Print)
IS  - 0371-0874 (Linking)
VI  - 63
IP  - 6
DP  - 2011 Dec 25
TI  - [The role and mechanism of high expression of cyclin B2 in MEN1 insulinoma].
PG  - 555-64
AB  - Multiple endocrine neoplasia type 1 (MEN1) is a dominantly inherited tumor 
      syndrome characterized by development of various combinations of tumors in 
      multiple endocrine glands, including the pituitary, parathyroid or pancreas. MEN1 
      results from mutations in tumor suppressor gene Men1, which encodes nuclear 
      protein menin. Menin has been shown to preferentially repress cell proliferation 
      in endocrine tissues including pancreatic beta cells. Herein, the present study 
      was to explore the potential mechanisms underlying menin in repressing cell 
      proliferation in mice MEN1 insulinoma. In the Gene Set Enrichment Analysis 
      (GSEA), Ccnb2 (encoding cyclin B2) was up-regulated in pancreatic islets of 
      Men1-excised mice after 14-day tamoxifen-feeding. Immunofluorescence with 
      antibody against cyclin B2 revealed that the expression of cyclin B2 was greatly 
      increased in MEN1 insulinoma. In Men1(-/-) cells, Men1 ablation leaded to an 
      increase in cyclin B2 expression. Immunofluorescent staining by phospho-H3S10 
      antibody revealed the increasing number of Men1(-/-) cells in mitosis. Cells were 
      seeded at a density of 5 x 10(4), then counted on day 2, 4 and 6, and the cell 
      growth curve revealed Men1 ablation increased the cell proliferation. In 
      contrast, knockdown of cyclin B2 by shRNA diminished the number of cells in 
      mitosis and reduced cell proliferation. Further, chromatin immunoprecipitation 
      (ChIP) assay indicated that menin affected the histone modification of the 
      promoter of Ccnb2 by reducing the level of histone H3 lysine 4 tri-methylation 
      (H3K4me3) and histone H3 acetylation but not affecting the level of histone H3 
      lysine 9 tri-methylation (H3K9me3) or histone H3 lysine 27 tri-methylation 
      (H3K27me3). Our results suggest that menin may inhibit MEN1 insulinoma by 
      suppressing cyclin B2 expression via histone modification.
FAU - Wu, Ting
AU  - Wu T
AD  - Department of Basic Medical Sciences, Medical College, Xiamen University, Xiamen 
      361005, China. wuting78@yahoo.com.cn
FAU - Huang, Xiao-Hua
AU  - Huang XH
LA  - chi
PT  - English Abstract
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Sheng Li Xue Bao
JT  - Sheng li xue bao : [Acta physiologica Sinica]
JID - 20730130R
RN  - 0 (Ccnb2 protein, mouse)
RN  - 0 (Cyclin B2)
RN  - 0 (Histones)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Animals
MH  - Cell Proliferation
MH  - Cyclin B2/genetics/*metabolism
MH  - Histones/metabolism
MH  - Insulinoma/*metabolism/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Mutation
MH  - Pancreatic Neoplasms/*metabolism/pathology
MH  - Proto-Oncogene Proteins/*genetics
EDAT- 2011/12/24 06:00
MHDA- 2013/02/22 06:00
CRDT- 2011/12/24 06:00
PHST- 2011/12/24 06:00 [entrez]
PHST- 2011/12/24 06:00 [pubmed]
PHST- 2013/02/22 06:00 [medline]
PST - ppublish
SO  - Sheng Li Xue Bao. 2011 Dec 25;63(6):555-64.