PMID- 19208834
OWN - NLM
STAT- MEDLINE
DCOM- 20090320
LR  - 20211028
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 69
IP  - 5
DP  - 2009 Mar 1
TI  - Recapitulation of pancreatic neuroendocrine tumors in human multiple endocrine 
      neoplasia type I syndrome via Pdx1-directed inactivation of Men1.
PG  - 1858-66
LID - 10.1158/0008-5472.CAN-08-3662 [doi]
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal syndrome caused by 
      mutations in the MEN1 tumor suppressor gene. Whereas the protein product of MEN1, 
      menin, is ubiquitously expressed, somatic loss of the remaining wild-type MEN1 
      allele results in tumors primarily in parathyroid, pituitary, and endocrine 
      pancreas. To understand the endocrine specificity of the MEN1 syndrome, we 
      evaluated biallelic loss of Men1 by inactivating Men1 in pancreatic progenitor 
      cells using the Cre-lox system. Men1 deletion in progenitor cells that 
      differentiate into exocrine and endocrine pancreas did not affect normal pancreas 
      morphogenesis and development. However, mice having homozygous inactivation of 
      the Men1 in pancreas developed endocrine tumors with no exocrine tumor 
      manifestation, recapitulating phenotypes seen in the MEN1 patients. In the 
      absence of menin, the endocrine pancreas showed increase in cell proliferation, 
      vascularity, and abnormal vascular structures; such changes were lacking in 
      exocrine pancreas. Further analysis revealed that these endocrine manifestations 
      were associated with up-regulation in vascular endothelial growth factor 
      expression in both human and mouse MEN1 pancreatic endocrine tumors. Together, 
      these data suggest the presence of cell-specific factors for menin and a 
      permissive endocrine environment for MEN1 tumorigenesis in endocrine pancreas. 
      Based on our analysis, we propose that menin's ability to maintain cellular and 
      microenvironment integrity might explain the endocrine- restrictive nature of the 
      MEN1 syndrome.
FAU - Shen, H-C Jennifer
AU  - Shen HC
AD  - Tumor Angiogenesis Section, Surgery Branch, National Cancer Institute, Bethesda, 
      Maryland 20892, USA.
FAU - He, Mei
AU  - He M
FAU - Powell, Anathea
AU  - Powell A
FAU - Adem, Asha
AU  - Adem A
FAU - Lorang, Dominique
AU  - Lorang D
FAU - Heller, Charles
AU  - Heller C
FAU - Grover, Amelia C
AU  - Grover AC
FAU - Ylaya, Kris
AU  - Ylaya K
FAU - Hewitt, Stephen M
AU  - Hewitt SM
FAU - Marx, Stephen J
AU  - Marx SJ
FAU - Spiegel, Allen M
AU  - Spiegel AM
FAU - Libutti, Steven K
AU  - Libutti SK
LA  - eng
GR  - Z01 SC010368-08/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20090210
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Homeodomain Proteins)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (pancreatic and duodenal homeobox 1 protein)
SB  - IM
MH  - Animals
MH  - Cell Proliferation
MH  - Homeodomain Proteins/*physiology
MH  - Humans
MH  - Islets of Langerhans/blood supply
MH  - Mice
MH  - Multiple Endocrine Neoplasia Type 1/*etiology
MH  - Neuroendocrine Tumors/*etiology
MH  - Pancreatic Neoplasms/*etiology
MH  - Proto-Oncogene Proteins/*physiology
MH  - Trans-Activators/*physiology
MH  - Vascular Endothelial Growth Factor A/physiology
PMC - PMC3879686
MID - NIHMS539944
COIS- Conflict of Interest Statement: None declared.
EDAT- 2009/02/12 09:00
MHDA- 2009/03/21 09:00
PMCR- 2014/01/03
CRDT- 2009/02/12 09:00
PHST- 2009/02/12 09:00 [entrez]
PHST- 2009/02/12 09:00 [pubmed]
PHST- 2009/03/21 09:00 [medline]
PHST- 2014/01/03 00:00 [pmc-release]
AID - 0008-5472.CAN-08-3662 [pii]
AID - 10.1158/0008-5472.CAN-08-3662 [doi]
PST - ppublish
SO  - Cancer Res. 2009 Mar 1;69(5):1858-66. doi: 10.1158/0008-5472.CAN-08-3662. Epub 
      2009 Feb 10.