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The Nuclear Receptor Corepressor (NCOR1) is a Tumor Promoter in a Mouse Model of Thyroid Cancer

Wednesday, October 10, 2012 — Poster Session II

Noon – 2:00 p.m

Natcher Conference Center, Building 45




  • L Fozzatti
  • JW Park
  • MC Willingham
  • SY Cheng


Follicular thyroid carcinoma (FTC) is one of the most common thyroid malignancies in the USA. However, the precise mechanisms underlying thyroid cancer remain unclear. Mice harboring a dominant-negative mutant thyroid hormone receptor (TR) β (denoted as PV; ThrbPV mice) spontaneously develop FTC similar to human cancer. To evaluate the role of NCOR1 in thyroid carcinogenesis in vivo we crossed ThrbPV mice with mice expressing a mutant Ncor1 allele (Ncor1ΔID mice) that cannot recruit wild-type TR or PV mutant (ThrbPV/PVNcor1ΔID/ΔID mice). ThrbPV/PVNcor1ΔID/ΔID mice exhibited increased survival, decreased thyroid tumor growth and delayed tumor progression. Further analyses indicated that NCOR1ΔID induced marked decreases in thyroid tumor cell proliferation, at least in part, due to decreased expression of key regulators of the cell cycle. Lack of association of PV with NCOR1ΔID led to a stronger interaction of PV with the tumor suppressor p53 in thyroids of ThrbPV/PVNcor1ΔID/ΔID than in ThrbPV/PVNcor1+/+ mice, leading to the activation of p53 to increase expression of p21 to decrease tumor cell proliferation. Thus, stabilization of p53 by a mutated TRβ is critical in the activity of p53 and represents a novel oncogenic mechanism that could contribute to the thyroid carcinogenesis in the ThrbPV mice.

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