期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 177, 期 4, 页码 1969-1976出版社
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2010.100138
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资金
- Helsinki Biomedical Graduate School, the Academy of Finland [6302352]
- Sigrid Juselius Foundation [4701169]
- Finnish Cancer Organizations
- Cancer Society of Finland [4700325, 4702054]
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 MP 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. (Am J Pathol 2010, 177:1969-1976; DOI: 10.2353/ajpath.2010.100138)
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