PMID- 18310289
OWN - NLM
STAT- MEDLINE
DCOM- 20080508
LR  - 20080303
IS  - 1351-0088 (Print)
IS  - 1351-0088 (Linking)
VI  - 15
IP  - 1
DP  - 2008 Mar
TI  - Deregulation of anti-Mullerian hormone/BMP and transforming growth factor-beta 
      pathways in Leydig cell lesions developed in male heterozygous multiple endocrine 
      neoplasia type 1 mutant mice.
PG  - 217-27
LID - 10.1677/ERC-06-0046 [doi]
AB  - Multiple endocrine neoplasia type 1 (MEN1) results from the mutation of the 
      predisposing gene, MEN1. Heterozygous Men1 mutant mice previously generated by 
      several laboratories, including ours, mimic largely MEN1 pathology. 
      Interestingly, our heterozygous Men1 mutant mice exhibit not only the endocrine 
      tumours commonly seen in MEN1 patients, but also Leydig cell tumours (LCT) with 
      high frequency, accompanied systematically by loss of the wild-type Men1 allele. 
      As there exists a similarity of tumour phenotype between these mice and those 
      mutated for the components of anti-Mullerian hormone (AMH)/bone morphogenic 
      protein (BMP) pathway belonging to transforming growth factor-beta (TGF-beta) 
      family, we investigated the expression and the activity of this pathway, known to 
      have an important biological role in Leydig cells. Here, we report that the 
      expression of AMH receptor type 2 is reduced in Men1 LCTs. Both immunostaining 
      and western blot analyses also demonstrate a markedly decreased nuclear 
      expression of Smad1, 3, 4 and 5 in the tumours. More interestingly, we show that 
      the reconstituted menin expression in Men1-deficient Leydig cells derived from 
      LCTs can significantly increase the transcriptional activity of a BMP pathway 
      target promoter, XVent2. Furthermore, we found that the expression of p18, p27 
      and cyclin dependant kinase 4 (Cdk4), targets of TGF-beta pathways, is altered in 
      the Leydig cell lesions. Our data provide the evidence of the deregulation of 
      AMH/BMP and TGF-beta pathways in mouse Men1 LCTs, highlighting their involvement 
      in tumorigenesis of Leydig cells due to Men1 inactivation.
FAU - Hussein, Nader
AU  - Hussein N
AD  - Universite Claude Bernard Lyon, Lyon, France.
FAU - Lu, JieLi
AU  - Lu J
FAU - Casse, Huguette
AU  - Casse H
FAU - Fontaniere, Sandra
AU  - Fontaniere S
FAU - Morera, Anne-Marie
AU  - Morera AM
FAU - Guittot, Severine Mazaud
AU  - Guittot SM
FAU - Calender, Alain
AU  - Calender A
FAU - Di Clemente, Nathalie
AU  - Di Clemente N
FAU - Zhang, Chang X
AU  - Zhang CX
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Endocr Relat Cancer
JT  - Endocrine-related cancer
JID - 9436481
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p18)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Peptide)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - 0 (Smad Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (anti-Mullerian hormone receptor)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - 80497-65-0 (Anti-Mullerian Hormone)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Anti-Mullerian Hormone/*metabolism
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Bone Morphogenetic Proteins/*metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p18/metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p27/metabolism
MH  - Heterozygote
MH  - Immunoenzyme Techniques
MH  - Immunoprecipitation
MH  - Leydig Cell Tumor/*metabolism/pathology
MH  - Luciferases/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Multiple Endocrine Neoplasia Type 1/*metabolism/pathology
MH  - Plasmids
MH  - Proto-Oncogene Proteins/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, Peptide/metabolism
MH  - Receptors, Transforming Growth Factor beta/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Smad Proteins/metabolism
MH  - Transforming Growth Factor beta/*metabolism
EDAT- 2008/03/04 09:00
MHDA- 2008/05/09 09:00
CRDT- 2008/03/04 09:00
PHST- 2008/03/04 09:00 [pubmed]
PHST- 2008/05/09 09:00 [medline]
PHST- 2008/03/04 09:00 [entrez]
AID - 15/1/217 [pii]
AID - 10.1677/ERC-06-0046 [doi]
PST - ppublish
SO  - Endocr Relat Cancer. 2008 Mar;15(1):217-27. doi: 10.1677/ERC-06-0046.