Format

Send to:

Choose Destination
See comment in PubMed Commons below
Steroids. 2011 Aug;76(9):885-91. doi: 10.1016/j.steroids.2011.03.016. Epub 2011 Apr 5.

Extranuclear signaling of mutated thyroid hormone receptors in promoting metastatic spread in thyroid carcinogenesis.

Author information

  • 1Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264, USA.

Abstract

Thyroid hormone receptors (TRs) mediate the critical activities of the thyroid hormone (T3) in growth, development, and differentiation. Decreased expression and/or somatic mutations of TRs have been shown to be associated with several types of human cancers including liver, breast, lung, and thyroid. A direct demonstration that TRβ mutants could function as oncogenes is evidenced by the spontaneous development of follicular thyroid carcinoma similar to human cancer in a knockin mouse model harboring a mutated TRβ (denoted as PV; Thrb(PV/PV) mice). PV is a dominant negative mutation identified in a patient with resistance to thyroid hormone. Analysis of altered gene expression and molecular studies of thyroid carcinogenesis in Thrb(PV/PV) mice show that the oncogenic activity of PV is mediated by both nucleus-initiated transcription and extranuclear actions to alter gene expression and signaling transduction activity. This article focuses on recent findings of novel extranuclear actions of PV that affect signaling cascades and thereby the invasiveness, migration, and motility of thyroid tumor cells. These findings have led to identification of potential molecular targets for treatment of metastatic thyroid cancer.

Published by Elsevier Inc.

PMID:
21473875
[PubMed - indexed for MEDLINE]
PMCID:
PMC3129395
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk