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

I H Chan1, M L Privalsky

  • 1Department of Microbiology, College of Biological Sciences, University of California at Davis, Davis, CA 95616, USA.

Oncogene
|September 15, 2009
PubMed

Insights

Mutated thyroid hormone receptors (TRs) in liver cancer (HCC) alter their gene targets, acting as oncoproteins. These cancer-associated TR mutants gain new functions, driving tumor development.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Thyroid hormone receptors (TRs) are crucial transcription factors regulating physiology and development.
  • TR mutations are frequently found in cancers, particularly hepatocellular carcinoma (HCC).

Purpose of the Study:

  • To investigate how mutations in TRs from HCC alter their target gene repertoire.
  • To understand the role of altered TR function in hepatocellular carcinoma pathogenesis.

Main Methods:

  • Stable cell transformants were created using HCC-derived TR mutants.
  • Expression array analysis was employed to compare gene expression profiles.

Main Results:

  • HCC-TR mutants exhibited a distinct target gene repertoire compared to wild-type TRs.
  • Mutant TRs regulated a subset of wild-type TR targets and gained the ability to regulate novel genes.
  • HCC-TR mutants could both activate and repress gene expression, not just repress.

Conclusions:

  • TR mutants in HCC possess altered transcriptional outputs and target gene profiles.
  • These alterations in TR function likely contribute to cancer development (neoplasia).

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