期刊
ONCOGENE
卷 29, 期 13, 页码 1909-1919出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2009.476
关键词
thyroid cancer; mouse model; mutations of thyroid hormone receptors
资金
- Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health
- NATIONAL CANCER INSTITUTE [ZIABC011191, ZIABC008752] Funding Source: NIH RePORTER
Aberrant expression and mutations of thyroid hormone receptor genes (TRs) are closely associated with several types of human cancers. To test the hypothesis that TRs could function as tumor suppressors, we took advantage of mice with deletion of all functional TRs (TR alpha 1(-/-)TR beta(-/-) mice). As these mice aged, they spontaneously developed follicular thyroid carcinoma with pathological progression from hyperplasia to capsular invasion, vascular invasion, anaplasia and metastasis to the lung, similar to human thyroid cancer. Detailed molecular analysis revealed that known tumor promoters such as pituitary tumor-transforming gene were activated and tumor suppressors such as peroxisome proliferator-activated receptor gamma and p53 were suppressed during carcinogenesis. In addition, consistent with the human cancer, AKT-mTOR-p70(S6K) signaling and vascular growth factor and its receptor were activated to facilitate tumor progression. This report presents in vivo evidence that functional loss of both TR alpha 1 and TR beta genes promotes tumor development and metastasis. Thus, TRs could function as tumor suppressors in a mouse model of metastatic follicular thyroid cancer. Oncogene (2010) 29, 1909-1919; doi:10.1038/onc.2009.476; published online 11 January 2010
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