Thyroid hormone receptor mutants implicated in human hepatocellular carcinoma display an altered target gene repertoire.

ABSTRACT: Thyroid hormone receptors (TRs) are hormone-regulated transcription factors that control multiple aspects of normal physiology and development. Mutations in TRs have been identified at high frequency in certain cancers, including human hepatocellular carcinomas (HCCs). The majority of HCC-TR mutants bear lesions within their DNA recognition domains, and we have hypothesized that these lesions change the mutant receptors' target gene repertoire in a way crucial to their function as oncoproteins. Using stable cell transformants and expression array analysis, we determined that mutant TRs isolated from two different HCCs do, as hypothesized, display a target gene repertoire distinct from that of their normal TR progenitors. Only a subset of genes regulated by wild-type TRs was regulated by th

SUBMITTER: Chan IH 

PROVIDER: S-EPMC2787677 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature