PMID- 20663219
OWN - NLM
STAT- MEDLINE
DCOM- 20110203
LR  - 20211020
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 10
DP  - 2010 Jul 27
TI  - Characterisation of prostate cancer lesions in heterozygous Men1 mutant mice.
PG  - 395
LID - 10.1186/1471-2407-10-395 [doi]
AB  - BACKGROUND: Mutations of the MEN1 gene predispose to multiple endocrine neoplasia 
      type 1 (MEN1) syndrome. Our group and others have shown that Men1 disruption in 
      mice recapitulates MEN1 pathology. Intriguingly, rare lesions in 
      hormone-dependent tissues, such as prostate and mammary glands, were also 
      observed in the Men1 mutant mice. METHODS: To study the occurrence of prostate 
      lesions, we followed a male mouse cohort of 47 Men1+/- mice and 23 age-matched 
      control littermates, starting at 18 months of age, and analysed the prostate 
      glands from the cohort. RESULTS: Six Men1+/- mice (12.8%) developed prostate 
      cancer, including two adenocarcinomas and four in situ carcinomas, while none of 
      the control mice developed cancerous lesions. The expression of menin encoded by 
      the Men1 gene was found to be drastically reduced in all carcinomas, and partial 
      LOH of the wild-type Men1 allele was detected in three of the five analysed 
      lesions. Using immunostaining for the androgen receptor and p63, a basal 
      epithelial cell marker, we demonstrated that the menin-negative prostate cancer 
      cells did not display p63 expression and that the androgen receptor was expressed 
      but more heterogeneous in these lesions. Furthermore, our data showed that the 
      expression of the cyclin-dependent kinase inhibitor CDKN1B (p27), a Men1 target 
      gene known to be inactivated during prostate cell tumorigenesis, was notably 
      decreased in the prostate cancers that developed in the mutant mice. CONCLUSION: 
      Our work suggests the possible involvement of Men1 inactivation in the 
      tumorigenesis of the prostate gland.
FAU - Seigne, Christelle
AU  - Seigne C
AD  - CNRS UMR5201, Laboratoire de Genetique Moleculaire, Signalisation et Cancer, 
      Centre Leon Berard, Lyon F-69008, France.
FAU - Fontaniere, Sandra
AU  - Fontaniere S
FAU - Carreira, Christine
AU  - Carreira C
FAU - Lu, Jieli
AU  - Lu J
FAU - Tong, Wei-Ming
AU  - Tong WM
FAU - Fontaniere, Bernard
AU  - Fontaniere B
FAU - Wang, Zhao-Qi
AU  - Wang ZQ
FAU - Zhang, Chang Xian
AU  - Zhang CX
FAU - Frappart, Lucien
AU  - Frappart L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100727
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Androgen)
RN  - 0 (Trans-Activators)
RN  - 0 (Trp63 protein, mouse)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
SB  - IM
MH  - Adenocarcinoma/*genetics/*pathology
MH  - Aging
MH  - Animals
MH  - Blotting, Southern
MH  - Cyclin-Dependent Kinase Inhibitor p27/metabolism
MH  - Heterozygote
MH  - Immunoenzyme Techniques
MH  - *Loss of Heterozygosity
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Phosphoproteins/metabolism
MH  - Prostatic Neoplasms/*genetics/*pathology
MH  - Proto-Oncogene Proteins/*physiology
MH  - Receptors, Androgen/metabolism
MH  - Trans-Activators/metabolism
PMC - PMC2920881
EDAT- 2010/07/29 06:00
MHDA- 2011/02/04 06:00
PMCR- 2010/07/27
CRDT- 2010/07/29 06:00
PHST- 2009/12/11 00:00 [received]
PHST- 2010/07/27 00:00 [accepted]
PHST- 2010/07/29 06:00 [entrez]
PHST- 2010/07/29 06:00 [pubmed]
PHST- 2011/02/04 06:00 [medline]
PHST- 2010/07/27 00:00 [pmc-release]
AID - 1471-2407-10-395 [pii]
AID - 10.1186/1471-2407-10-395 [doi]
PST - epublish
SO  - BMC Cancer. 2010 Jul 27;10:395. doi: 10.1186/1471-2407-10-395.