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Receptor Gone Rogue: Investigating Localization of a Cancerous Thyroid Hormone Receptor
Barbeau, Michelle
Barbeau, Michelle
Abstract
Thyroid hormone receptors play a crucial role in regulating differentiation, growth and development in response to thyroid hormone, and mutations in these receptors can have severe medical consequences ranging from endocrine dysfunction to cancer. Tumors of patients with hepatocellular carcinoma (HCC) display a high incidence of mutant thyroid hormone receptors (TRs), and one such mutant is TRα1 (K74E, A264V). The binding partners and gene targets of this mutant have been characterized, but the role of intracellular localization in the pathogenesis of TRα1 (K74E, A264V) has not yet been determined. Here, it was observed that the mutant receptor has a tendency to aggregate when transfected into HeLa (human) cells. Fluorescence microscopy was used to determine the extent of this aggregation. The data showed that the TR mutant displays a significantly higher frequency of nuclear and cytosolic aggregates. Furthermore, it induces a significantly higher amount of nuclear and cytosolic aggregates in the wild type TR when coexpressed in the cell, and this effect increases with increasing amounts of transfected mutant-containing plasmid. These results highlight a potential dominant-negative of TRα1 (K74E, A264V) effect as it pertains to localization and offer a new layer of understanding to the altered activity of this mutant TR during the development of cancer.
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2017-05-01
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Biology