PMID- 28273452
OWN - NLM
STAT- MEDLINE
DCOM- 20171128
LR  - 20181113
IS  - 2211-1247 (Electronic)
VI  - 18
IP  - 10
DP  - 2017 Mar 7
TI  - Enhancer-Mediated Oncogenic Function of the Menin Tumor Suppressor in Breast 
      Cancer.
PG  - 2359-2372
LID - S2211-1247(17)30206-1 [pii]
LID - 10.1016/j.celrep.2017.02.025 [doi]
AB  - While the multiple endocrine neoplasia type 1 (MEN1) gene functions as a tumor 
      suppressor in a variety of cancer types, we explored its oncogenic role in breast 
      tumorigenesis. The MEN1 gene product menin is involved in H3K4 trimethylation and 
      co-activates transcription. We integrated ChIP-seq and RNA-seq data to identify 
      menin target genes. Our analysis revealed that menin-dependent target gene 
      promoters display looping to distal enhancers that are bound by menin, FOXA1 and 
      GATA3. In this fashion, MEN1 co-regulates a proliferative breast cancer-specific 
      gene expression program in ER(+) cells. In primary mammary cells, MEN1 exerts an 
      anti-proliferative function by regulating a distinct expression signature. Our 
      findings clarify the cell-type-specific functions of MEN1 and inform the 
      development of menin-directed treatments for breast cancer.
CI  - Copyright (c) 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Dreijerink, Koen M A
AU  - Dreijerink KMA
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, 450 Brookline Avenue, Boston 02215, MA, USA; Center for Functional Cancer 
      Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline 
      Avenue, Boston 02215, MA, USA.
FAU - Groner, Anna C
AU  - Groner AC
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, 450 Brookline Avenue, Boston 02215, MA, USA; Center for Functional Cancer 
      Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline 
      Avenue, Boston 02215, MA, USA.
FAU - Vos, Erica S M
AU  - Vos ESM
AD  - Hubrecht Institute-KNAW and University Medical Center, Uppsalalaan 8, 3584 CT 
      Utrecht, the Netherlands.
FAU - Font-Tello, Alba
AU  - Font-Tello A
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, 450 Brookline Avenue, Boston 02215, MA, USA; Center for Functional Cancer 
      Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline 
      Avenue, Boston 02215, MA, USA.
FAU - Gu, Lei
AU  - Gu L
AD  - Division of Newborn Medicine, Children's Hospital Boston and Department of Cell 
      Biology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
FAU - Chi, David
AU  - Chi D
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, 450 Brookline Avenue, Boston 02215, MA, USA; Center for Functional Cancer 
      Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline 
      Avenue, Boston 02215, MA, USA.
FAU - Reyes, Jaime
AU  - Reyes J
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, 450 Brookline Avenue, Boston 02215, MA, USA.
FAU - Cook, Jennifer
AU  - Cook J
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, 450 Brookline Avenue, Boston 02215, MA, USA; Center for Functional Cancer 
      Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline 
      Avenue, Boston 02215, MA, USA.
FAU - Lim, Elgene
AU  - Lim E
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, 450 Brookline Avenue, Boston 02215, MA, USA; Center for Functional Cancer 
      Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline 
      Avenue, Boston 02215, MA, USA.
FAU - Lin, Charles Y
AU  - Lin CY
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, 450 Brookline Avenue, Boston 02215, MA, USA.
FAU - de Laat, Wouter
AU  - de Laat W
AD  - Hubrecht Institute-KNAW and University Medical Center, Uppsalalaan 8, 3584 CT 
      Utrecht, the Netherlands.
FAU - Rao, Prakash K
AU  - Rao PK
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, 450 Brookline Avenue, Boston 02215, MA, USA; Center for Functional Cancer 
      Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline 
      Avenue, Boston 02215, MA, USA.
FAU - Long, Henry W
AU  - Long HW
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, 450 Brookline Avenue, Boston 02215, MA, USA; Center for Functional Cancer 
      Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline 
      Avenue, Boston 02215, MA, USA.
FAU - Brown, Myles
AU  - Brown M
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, 450 Brookline Avenue, Boston 02215, MA, USA; Center for Functional Cancer 
      Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline 
      Avenue, Boston 02215, MA, USA. Electronic address: myles_brown@dfci.harvard.edu.
LA  - eng
GR  - P01 CA080111/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (FOXA1 protein, human)
RN  - 0 (GATA3 Transcription Factor)
RN  - 0 (Hepatocyte Nuclear Factor 3-alpha)
RN  - 0 (Histones)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 4TI98Z838E (Estradiol)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Breast Neoplasms/*genetics/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Enhancer Elements, Genetic/*genetics
MH  - Estradiol/pharmacology
MH  - Estrogen Receptor alpha/metabolism
MH  - Female
MH  - GATA3 Transcription Factor/metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - Genomics
MH  - Hepatocyte Nuclear Factor 3-alpha/metabolism
MH  - Histones/metabolism
MH  - Humans
MH  - Lysine/metabolism
MH  - Methylation
MH  - *Oncogenes
MH  - Promoter Regions, Genetic
MH  - Protein Binding/drug effects
MH  - Proto-Oncogene Proteins/*genetics
MH  - Transcription, Genetic
PMC - PMC5609449
MID - NIHMS852390
OTO - NOTNLM
OT  - MEN1
OT  - breast cancer
OT  - enhancer
OT  - epigenetics
OT  - histone H3K4 trimethylation
OT  - menin
OT  - oncogene
OT  - transcription
OT  - tumor suppressor
EDAT- 2017/03/09 06:00
MHDA- 2017/11/29 06:00
PMCR- 2017/09/22
CRDT- 2017/03/09 06:00
PHST- 2016/05/11 00:00 [received]
PHST- 2016/12/17 00:00 [revised]
PHST- 2017/02/07 00:00 [accepted]
PHST- 2017/03/09 06:00 [entrez]
PHST- 2017/03/09 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2017/09/22 00:00 [pmc-release]
AID - S2211-1247(17)30206-1 [pii]
AID - 10.1016/j.celrep.2017.02.025 [doi]
PST - ppublish
SO  - Cell Rep. 2017 Mar 7;18(10):2359-2372. doi: 10.1016/j.celrep.2017.02.025.