PMID- 22915754
OWN - NLM
STAT- MEDLINE
DCOM- 20121221
LR  - 20230610
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 72
IP  - 19
DP  - 2012 Oct 1
TI  - MEN1 gene replacement therapy reduces proliferation rates in a mouse model of 
      pituitary adenomas.
PG  - 5060-8
LID - 10.1158/0008-5472.CAN-12-1821 [doi]
AB  - Multiple endocrine neoplasia type 1 (MEN1) is characterized by the combined 
      occurrence of pituitary, pancreatic, and parathyroid tumors showing loss of 
      heterozygosity in the putative tumor suppressor gene MEN1. This gene encodes the 
      protein menin, the overexpression of which inhibits cell proliferation in vitro. 
      In this study, we conducted a preclinical evaluation of MEN1 gene therapy in 
      pituitary tumors of Men1(+/-) mice, using a recombinant nonreplicating adenoviral 
      serotype 5 vector that contained the murine Men1 cDNA under control of a 
      cytomegalovirus promoter (Men1.rAd5). Pituitary tumors in 55 Men1(+/-) female 
      mice received a transauricular intratumoral injection of Men1.rAd5 or control 
      treatments, followed by 5-bromo-2-deoxyuridine (BrdUrd) in drinking water for 
      four weeks before magnetic resonance imaging (MRI) and immunohistochemical 
      analysis. Immediate procedure-related and 4-week mortalities were similar in all 
      groups, indicating that the adenoviral gene therapy was not associated with a 
      higher mortality. Menin expression was higher in the Men1.rAd5-treated mice when 
      compared with other groups. Daily proliferation rates assessed by BrdUrd 
      incorporation were reduced significantly in Men1.rAd5-injected tumors relative to 
      control-treated tumors. In contrast, apoptotic rates, immune T-cell response, and 
      tumor volumes remained similar in all groups. Our findings establish that MEN1 
      gene replacement therapy can generate menin expression in pituitary tumors, and 
      significantly reduce tumor cell proliferation.
CI  - (c)2012 AACR.
FAU - Walls, Gerard V
AU  - Walls GV
AD  - Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre 
      for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Headington, 
      Oxford, United Kingdom.
FAU - Lemos, Manuel C
AU  - Lemos MC
FAU - Javid, Mahsa
AU  - Javid M
FAU - Bazan-Peregrino, Miriam
AU  - Bazan-Peregrino M
FAU - Jeyabalan, Jeshmi
AU  - Jeyabalan J
FAU - Reed, Anita A C
AU  - Reed AA
FAU - Harding, Brian
AU  - Harding B
FAU - Tyler, Damian J
AU  - Tyler DJ
FAU - Stuckey, Daniel J
AU  - Stuckey DJ
FAU - Piret, Sian
AU  - Piret S
FAU - Christie, Paul T
AU  - Christie PT
FAU - Ansorge, Olaf
AU  - Ansorge O
FAU - Clarke, Kieran
AU  - Clarke K
FAU - Seymour, Len
AU  - Seymour L
FAU - Thakker, Rajesh V
AU  - Thakker RV
LA  - eng
GR  - 913/MSS_/Multiple Sclerosis Society/United Kingdom
GR  - RG/07/004/22659/BHF_/British Heart Foundation/United Kingdom
GR  - 11339/CRUK_/Cancer Research UK/United Kingdom
GR  - G0601490/MRC_/Medical Research Council/United Kingdom
GR  - G0501780/76451/MRC_/Medical Research Council/United Kingdom
GR  - G9825289(67320)/MRC_/Medical Research Council/United Kingdom
GR  - G0501780/MRC_/Medical Research Council/United Kingdom
GR  - G9825289/MRC_/Medical Research Council/United Kingdom
GR  - 087332/Z/08/Z/WT_/Wellcome Trust/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
GR  - PS/02/002/14893/BHF_/British Heart Foundation/United Kingdom
GR  - FS/10/002/28078/BHF_/British Heart Foundation/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 - 20120821
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adenoma/genetics/metabolism/*therapy
MH  - Adenoviridae/genetics
MH  - Animals
MH  - *Cell Proliferation
MH  - *Disease Models, Animal
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors/genetics
MH  - HEK293 Cells
MH  - Humans
MH  - Immunohistochemistry
MH  - Magnetic Resonance Imaging
MH  - Mice
MH  - Mice, 129 Strain
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Pituitary Gland/diagnostic imaging/metabolism/pathology
MH  - Pituitary Neoplasms/genetics/metabolism/*therapy
MH  - Proto-Oncogene Proteins/*genetics/metabolism
MH  - Radiography
PMC - PMC3463502
MID - UKMS49784
OID - NLM: UKMS49784
EDAT- 2012/08/24 06:00
MHDA- 2012/12/22 06:00
PMCR- 2013/04/01
CRDT- 2012/08/24 06:00
PHST- 2012/08/24 06:00 [entrez]
PHST- 2012/08/24 06:00 [pubmed]
PHST- 2012/12/22 06:00 [medline]
PHST- 2013/04/01 00:00 [pmc-release]
AID - 0008-5472.CAN-12-1821 [pii]
AID - 10.1158/0008-5472.CAN-12-1821 [doi]
PST - ppublish
SO  - Cancer Res. 2012 Oct 1;72(19):5060-8. doi: 10.1158/0008-5472.CAN-12-1821. Epub 
      2012 Aug 21.