Back to Search
Start Over
Mice with Inactivation of Aryl Hydrocarbon Receptor-Interacting Protein (Aip) Display Complete Penetrance of Pituitary Adenomas with Aberrant ARNT Expression
- Source :
- The American Journal of Pathology. 177:1969-1976
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
Abstract
- Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene have been shown to predispose to pituitary adenoma predisposition, a condition characterized by growth hormone (GH)-secreting pituitary tumors. To study AIP-mediated tumorigenesis, we generated an Aip mouse model. Heterozygous mice developed normally but were prone to pituitary adenomas, in particular to those secreting GH. A complete loss of AIP was detected in these lesions, and full penetrance was reached at the age of 15 months. No excess of any other tumor type was found. Ki-67 analysis indicated that Aip-deficient tumors have higher proliferation rates compared with Aip-proficient tumors, suggesting a more aggressive disease. Similar to human AIP-deficient pituitary adenomas, immunohistochemical studies showed that expression of aryl hydrocarbon receptor nuclear translocator 1 or 2 (ARNT or ARNT2) protein was lost in the mouse tumors, suggesting that mechanisms of AIP-related tumorigenesis involve aberrant ARNT function. The Aip(+/-) mouse appears to be an excellent model for the respective human disease phenotype. This model constitutes a tool to further study AIP-associated pituitary tumorigenesis and may be potentially valuable in efforts to develop therapeutic strategies to treat pituitary adenomas.
- Subjects :
- Male
medicine.medical_specialty
Aryl hydrocarbon receptor nuclear translocator
Blotting, Western
Loss of Heterozygosity
Estrogen receptor
Biology
Gene mutation
medicine.disease_cause
Pathology and Forensic Medicine
Immunoenzyme Techniques
Mice
03 medical and health sciences
0302 clinical medicine
Pituitary adenoma
Internal medicine
medicine
Animals
Humans
RNA, Messenger
Cell Proliferation
030304 developmental biology
0303 health sciences
Reverse Transcriptase Polymerase Chain Reaction
Aryl Hydrocarbon Receptor Nuclear Translocator
Pituitary tumors
Intracellular Signaling Peptides and Proteins
medicine.disease
Aryl hydrocarbon receptor
Penetrance
3. Good health
Mice, Inbred C57BL
Endocrinology
030220 oncology & carcinogenesis
biology.protein
Cancer research
Female
Growth Hormone-Secreting Pituitary Adenoma
Carcinogenesis
Regular Articles
Subjects
Details
- ISSN :
- 00029440
- Volume :
- 177
- Database :
- OpenAIRE
- Journal :
- The American Journal of Pathology
- Accession number :
- edsair.doi.dedup.....b22bc17c9e0f65bc4ac392ede2c038c7