PMID- 23024266
OWN - NLM
STAT- MEDLINE
DCOM- 20130117
LR  - 20230710
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 153
IP  - 11
DP  - 2012 Nov
TI  - Proliferation rates of multiple endocrine neoplasia type 1 (MEN1)-associated 
      tumors.
PG  - 5167-79
LID - 10.1210/en.2012-1675 [doi]
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder 
      characterized by the combined occurrence of parathyroid and adrenocortical 
      tumors, and neuroendocrine tumors (NETs) of the pancreas and pituitary. The 
      pancreatic NETs are predominantly gastrinomas and insulinomas, and the pituitary 
      NETs are mostly prolactinomas and somatotrophinomas. We postulated that the 
      different types of pancreatic and pituitary NETs may be partly due to differences 
      in their proliferation rates, and we therefore assessed these in MEN1-associated 
      tumors and gonadal tumors that developed in mice deleted for an Men1 allele 
      (Men1(+/-)). To label proliferating cells in vivo, Men1(+/-) and wild-type 
      (Men1(+/+)) mice were given 5-bromo-2-deoxyuridine (BrdU) in drinking water from 
      1-12 wk, and tissue sections were immunostained using anti-BrdU and 
      hormone-specific antibodies. Proliferation in the tumors of Men1(+/-) mice was 
      significantly (P < 0.001) increased when compared with the corresponding normal 
      Men1(+/+) tissues. Pancreatic, pituitary and adrenocortical proliferation fitted 
      first- and second-order regression lines in Men1(+/+) tissues and Men1(+/-) 
      tumors, respectively, R(2) = 0.999. Apoptosis was similar in Men1(+/-) 
      pancreatic, pituitary, and parathyroid tumors when compared with corresponding 
      normal tissues, decreased in Men1(+/-) adrenocortical tumors, but increased in 
      Men1(+/-) gonadal tumors. Mathematical modeling of NET growth rates 
      (proliferation minus apoptosis rates) predicted that in Men1(+/-) mice, only 
      pancreatic beta-cells, pituitary lactotrophs and somatotrophs could develop into 
      tumors within a murine lifespan. Thus, our studies demonstrate that Men1(+/-) 
      tumors have low proliferation rates (<2%), second-order kinetics, and the higher 
      occurrence of insulinomas, prolactinomas, and somatotrophinomas in MEN1 is 
      consistent with a mathematical model for NET proliferation.
FAU - Walls, Gerard V
AU  - Walls GV
AD  - Academic Endocrine Unit, Nuffield Department of Clinical Medicine, University of 
      Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, United Kingdom.
FAU - Reed, Anita A C
AU  - Reed AA
FAU - Jeyabalan, Jeshmi
AU  - Jeyabalan J
FAU - Javid, Mahsa
AU  - Javid M
FAU - Hill, Nathan R
AU  - Hill NR
FAU - Harding, Brian
AU  - Harding B
FAU - Thakker, Rajesh V
AU  - Thakker RV
LA  - eng
GR  - G0501780/MRC_/Medical Research Council/United Kingdom
GR  - 087332/Z/08/Z/WT_/Wellcome Trust/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
GR  - 913/MSS_/Multiple Sclerosis Society/United Kingdom
GR  - G9825289/MRC_/Medical Research Council/United Kingdom
GR  - 913/DH_/Department of Health/United Kingdom
GR  - G1000467/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120928
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adrenal Cortex Neoplasms/genetics/metabolism/pathology
MH  - Animals
MH  - Apoptosis
MH  - *Cell Proliferation
MH  - Mice
MH  - Mice, Knockout
MH  - Multiple Endocrine Neoplasia Type 1/genetics/metabolism/*pathology
MH  - Neuroendocrine Tumors/genetics/metabolism/*pathology
MH  - Pancreatic Neoplasms/genetics/metabolism/pathology
MH  - Pituitary Neoplasms/genetics/metabolism/pathology
MH  - Proto-Oncogene Proteins/*genetics/metabolism
PMC - PMC4447856
EDAT- 2012/10/02 06:00
MHDA- 2013/01/18 06:00
PMCR- 2013/11/01
CRDT- 2012/10/02 06:00
PHST- 2012/10/02 06:00 [entrez]
PHST- 2012/10/02 06:00 [pubmed]
PHST- 2013/01/18 06:00 [medline]
PHST- 2013/11/01 00:00 [pmc-release]
AID - en.2012-1675 [pii]
AID - EN-12-1675 [pii]
AID - 10.1210/en.2012-1675 [doi]
PST - ppublish
SO  - Endocrinology. 2012 Nov;153(11):5167-79. doi: 10.1210/en.2012-1675. Epub 2012 Sep 
      28.