| Autor: |
Raitila, Anniina, Lehtonen, Heli J., Arola, Johanna, Heliövaara, Elina, Ahlsten, Manuel, Georgitsi, Marianthi, Jalanko, Anu, Paetau, Anders, Aaltonen, Lauri A., Karhu, Auli |
| Zdroj: |
American Journal of Pathology; October 2010, Vol. 177 Issue: 4 p1969-1976, 8p |
| Abstrakt: |
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 Aipmouse 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. |
| Databáze: |
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