PMID- 26871472
OWN - NLM
STAT- MEDLINE
DCOM- 20171204
LR  - 20200902
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 11
DP  - 2016 Mar 15
TI  - Loss of MEN1 activates DNMT1 implicating DNA hypermethylation as a driver of MEN1 
      tumorigenesis.
PG  - 12633-50
LID - 10.18632/oncotarget.7279 [doi]
AB  - Multiple endocrine neoplasia type 1 (MEN1) syndrome results from mutations in the 
      MEN1 gene and causes tumor formation via largely unknown mechanisms. Using a 
      novel genome-wide methylation analysis, we studied tissues from MEN1-parathyroid 
      tumors, Men1 knockout (KO) mice, and Men1 null mouse embryonic fibroblast (MEF) 
      cell lines. We demonstrated that inactivation of menin (the protein product of 
      MEN1) increases activity of DNA (cytosine-5)-methyltransferase 1 (DNMT1) by 
      activating retinoblastoma-binding protein 5 (Rbbp5). The increased activity of 
      DNMT1 mediates global DNA hypermethylation, which results in aberrant activation 
      of the Wnt/beta-catenin signaling pathway through inactivation of Sox regulatory 
      genes. Our study provides important insights into the role of menin in DNA 
      methylation and its impact on the pathogenesis of MEN1 tumor development.
FAU - Yuan, Ziqiang
AU  - Yuan Z
AD  - Department of Surgery, Albert Einstein College of Medicine, Bronx, New York, USA.
FAU - Sanchez Claros, Carmen
AU  - Sanchez Claros C
AD  - Department of Surgery, Albert Einstein College of Medicine, Bronx, New York, USA.
FAU - Suzuki, Masako
AU  - Suzuki M
AD  - Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, 
      USA.
FAU - Maggi, Elaine C
AU  - Maggi EC
AD  - Department of Surgery, Albert Einstein College of Medicine, Bronx, New York, USA.
FAU - Kaner, Justin D
AU  - Kaner JD
AD  - Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, 
      USA.
FAU - Kinstlinger, Noah
AU  - Kinstlinger N
AD  - Department of Surgery, Albert Einstein College of Medicine, Bronx, New York, USA.
FAU - Gorecka, Jolanta
AU  - Gorecka J
AD  - Department of Surgery, Albert Einstein College of Medicine, Bronx, New York, USA.
FAU - Quinn, Thomas J
AU  - Quinn TJ
AD  - Department of Surgery, Albert Einstein College of Medicine, Bronx, New York, USA.
FAU - Geha, Rula
AU  - Geha R
AD  - Department of Surgery, Albert Einstein College of Medicine, Bronx, New York, USA.
FAU - Corn, Amanda
AU  - Corn A
AD  - Department of Surgery, Albert Einstein College of Medicine, Bronx, New York, USA.
FAU - Pastoriza, Jessica
AU  - Pastoriza J
AD  - Department of Surgery, Albert Einstein College of Medicine, Bronx, New York, USA.
FAU - Jing, Qiang
AU  - Jing Q
AD  - Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, 
      USA.
FAU - Adem, Asha
AU  - Adem A
AD  - Department of Surgery, Albert Einstein College of Medicine, Bronx, New York, USA.
FAU - Wu, Hao
AU  - Wu H
AD  - Department of Surgery, Albert Einstein College of Medicine, Bronx, New York, USA.
FAU - Alemu, Girum
AU  - Alemu G
AD  - Department of Surgery, Albert Einstein College of Medicine, Bronx, New York, USA.
FAU - Du, Yi-Chieh
AU  - Du YC
AD  - Department of Pathology and Lab Medicine, Weill Cornell Medical College, New 
      York, New York, USA.
FAU - Zheng, Deyou
AU  - Zheng D
AD  - Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, 
      USA.
AD  - Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, 
      USA.
AD  - Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, 
      USA.
FAU - Greally, John M
AU  - Greally JM
AD  - Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, 
      USA.
AD  - Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, 
      USA.
AD  - Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York, 
      USA.
FAU - Libutti, Steven K
AU  - Libutti SK
AD  - Department of Surgery, Albert Einstein College of Medicine, Bronx, New York, USA.
AD  - Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, 
      USA.
LA  - eng
GR  - P30 DK041296/DK/NIDDK NIH HHS/United States
GR  - P50 CA174521/CA/NCI NIH HHS/United States
GR  - R01 CA170911/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (MEN1 protein, human)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1)
RN  - EC 2.1.1.37 (DNMT1 protein, human)
RN  - EC 2.1.1.37 (Dnmt1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Cell Transformation, Neoplastic/*genetics
MH  - DNA (Cytosine-5-)-Methyltransferase 1/*metabolism
MH  - DNA Methylation
MH  - Humans
MH  - Mice
MH  - Mice, Knockout
MH  - Multiple Endocrine Neoplasia Type 1/genetics/*metabolism
MH  - Proto-Oncogene Proteins/genetics/*metabolism
PMC - PMC4914310
OTO - NOTNLM
OT  - DNMT1
OT  - HELP-tagging
OT  - MEN1
OT  - Sox/Wnt/beta-catenin signaling pathway
OT  - global DNA methylation
COIS- CONFLICTS OF INTEREST We declare that we have no conflicts of interest.
EDAT- 2016/02/13 06:00
MHDA- 2017/12/05 06:00
PMCR- 2016/03/15
CRDT- 2016/02/13 06:00
PHST- 2015/10/12 00:00 [received]
PHST- 2016/01/24 00:00 [accepted]
PHST- 2016/02/13 06:00 [entrez]
PHST- 2016/02/13 06:00 [pubmed]
PHST- 2017/12/05 06:00 [medline]
PHST- 2016/03/15 00:00 [pmc-release]
AID - 7279 [pii]
AID - 10.18632/oncotarget.7279 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Mar 15;7(11):12633-50. doi: 10.18632/oncotarget.7279.