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Impaired nuclear translocation of CAR in hepatic preneoplastic lesions: Association with an attenuated CYP2B induction by phenobarbital
Author(s) -
Numazawa Satoshi,
Shindo Sawako,
Maruyama Keiji,
Chibana Fumika,
Kawahara Yosuke,
Ashino Takashi,
Tanaka Sachiko,
Yoshida Takemi
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.05.028
Subject(s) - constitutive androstane receptor , phenobarbital , transactivation , chromosomal translocation , cancer research , nuclear receptor , endocrinology , biology , medicine , gene , gene expression , transcription factor , biochemistry
Phenobarbital (PB) induction of CYP2B, a representative target gene of constitutive androstane receptor (CAR), has been observed to be attenuated in preneoplastic lesions of rat liver; however, molecular basis for this attenuation is poorly understood. In this report, we provide evidence indicating that the CAR expressed in the hepatic preneoplastic lesions of rats and mice was resistant to nuclear translocation and transactivation of the PB‐responsive enhancer module upon PB treatment. These observations suggest that the attenuation of the induction of CYP2B by PB in hepatic preneoplastic lesions is evidently a consequence of impaired nuclear translocation of CAR.