Back to Search
Start Over
Characterisation of prostate cancer lesions in heterozygous Men1 mutant mice
- Source :
- BMC Cancer, BMC Cancer, BioMed Central, 2010, 10 (1), pp.395. ⟨10.1186/1471-2407-10-395⟩, BMC Cancer, Vol 10, Iss 1, p 395 (2010), BMC Cancer, 2010, 10 (1), pp.395. ⟨10.1186/1471-2407-10-395⟩
- Publication Year :
- 2010
- Publisher :
- BioMed Central, 2010.
-
Abstract
- 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.
- Subjects :
- Male
Cancer Research
Aging
endocrine system diseases
Loss of Heterozygosity
medicine.disease_cause
Immunoenzyme Techniques
Prostate cancer
Mice
0302 clinical medicine
Prostate
MESH: Blotting, Southern
MESH: Aging
MESH: Animals
Multiple endocrine neoplasia
MESH: Heterozygote
0303 health sciences
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
3. Good health
Blotting, Southern
medicine.anatomical_structure
Oncology
Receptors, Androgen
030220 oncology & carcinogenesis
Adenocarcinoma
MESH: Receptors, Androgen
Cyclin-Dependent Kinase Inhibitor p27
Research Article
congenital, hereditary, and neonatal diseases and abnormalities
endocrine system
Heterozygote
MESH: Trans-Activators
[SDV.CAN]Life Sciences [q-bio]/Cancer
Biology
lcsh:RC254-282
MESH: Phosphoproteins
03 medical and health sciences
[SDV.CAN] Life Sciences [q-bio]/Cancer
MESH: Mice, Inbred C57BL
MESH: Cyclin-Dependent Kinase Inhibitor p27
Proto-Oncogene Proteins
medicine
Genetics
Animals
MEN1
MESH: Immunoenzyme Techniques
MESH: Mice
030304 developmental biology
MESH: Loss of Heterozygosity
MESH: Adenocarcinoma
Prostatic Neoplasms
medicine.disease
Phosphoproteins
MESH: Male
Androgen receptor
MESH: Proto-Oncogene Proteins
Mice, Inbred C57BL
MESH: Prostatic Neoplasms
Cancer research
Trans-Activators
CDKN1B
Carcinogenesis
Subjects
Details
- Language :
- English
- ISSN :
- 14712407
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- BMC Cancer
- Accession number :
- edsair.doi.dedup.....51164c1990eae71f84ee3975639ca5ae