Description of Invention: This technology describes a mouse model of thyroid cancer where the phosphatidy-linositol 3-kinase (Pl3K)-AKT/protein kinase B-signaling pathway is overactivated. These mice have a knock-in dominantly negative mutant thyroid hormone receptor beta gene (TRbetaPV mutant) that spontaneously develops thyroid cancer and distant metastasis similar to human follicular thyroid cancer. The thyroids of TRbetaPV mice exhibit extensive hyperplasia, which progresses to capsular invasion, vascular invasion, anaplasia, and ultimately, metastasis to distant organs. Consequently, this mouse model could be used as a preclinical model to understand genetic changes during cancer development and to identify potential molecular targets for the diagnosis, prevention, and treatment of cancer. For example, the inventors have used the TRbetaPV mice to show that the peroxisome proliferator-activated receptor gamma (PPARgamma) could function as a tumor suppressor in vivo and that the activation of the Pl3K-AKT signaling contributes to thyroid carcinogenesis and could be a potential therapeutic target in follicular thyroid carcinoma.
Identifying potential molecular targets for cancer diagnosis, prevention, and treatment.
Testing kinase inhibitors and other novel drugs being discover for the treatment of thyroid cancer.
Tools to understand the genetic changes during cancer development.
Advantages: This model provides the opportunity to study the alterations in gene regulation that occur during the progression and metastasis of thyroid carcinogenesis, not just the genes that control initial carcinogenesis.
Development Status: The technology is currently in the pre-clinical stage of development.
Inventors: Sheue-yann Cheng (NCI)
Patent Status: HHS, Reference No. E-208-2009/0
Research Tool -- Patent protection is not being pursued for this technology.
Furuya F, Lu C, Willingham MC, Cheng SY. Inhibition of phosphatidylinositol 3-kinase delays tumor progression and blocks metastatic spread in a mouse model of thyroid cancer. Carcinogenesis. 2007 Dec;28(12):2451-2458. [ PubMed: 17660507 ]
Kato Y, Ying H, Zhao L, Furuya F, Araki O, Willingham MC, Cheng SY. PPARgamma insufficiency promotes follicular thyroid carcinogenesis via activation of the nuclear factor-kappaB signaling pathway. Oncogene. 2006 May 4;25(19):2736-2747. [ PubMed: 16314832 ]
Suzuki H, Willingham MC, Cheng SY. Mice with a mutation in the thyroid hormone receptor beta gene spontaneously develop thyroid carcinoma: a mouse model of thyroid carcinogenesis. Thyroid. 2002 Nov;12(11):963-969. [ PubMed: 12490073 ]
Kaneshige M, Kaneshige K, Zhu X, Dace A, Garrett L, Carter TA, Kazlauskaite R, Pankratz DG, Wynshaw-Boris A, Refetoff S, Weintraub B, Willingham MC, Barlow C, Cheng S. Mice with a targeted mutation in the thyroid hormone beta receptor gene exhibit impaired growth and resistance to thyroid hormone. Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13209-13214. [ PubMed: 11069286 ]
Licensing Status: Available for licensing.
Portfolios: Devices/Instrumentation Cancer Cancer - Research Materials
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