ONCOGENIC ACTIONS OF THE NUCLEAR RECEPTOR COREPRESSOR (NCOR1) IN A MOUSE MODEL OF THYROID CANCER

FOZZATTI, LAURA; PARK JEONG WON; ZHAO LI; WILLINGHAM MARK C; CHENG SHEUE-YANN

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2013 vol. 8 p. 1 - 1

tudies have suggested that the nuclear receptor corepressor 1 (NCOR1) could play an important role in human cancers. However, the detailed molecular mechanisms by which it functions in vivo to affect cancer progression are not clear. The present study elucidated the in vivo actions of NCOR1 in carcinogenesis using a mouse model (ThrbPV/PV mice) that spontaneously develops thyroid cancer. ThrbPV/PV mice harbor a dominantly negative thyroid hormone receptor b (TRb) mutant (denoted as PV). We adopted the loss-of-the function approach by crossing ThrbPV mice with mice that globally express an NCOR1 mutant protein (NCOR1DID) in which the receptor interaction domains have been modified so that it cannot interact with the TRb, or PV, in mice. Remarkably, expression of NCOR1DID protein reduced thyroid tumor growth, markedly delayed tumor progression, and prolonged survival of ThrbPV/PVNcor1DID/DID mice. Tumor cell proliferation was inhibited by increased expression of cyclin-dependent kinase