Lost expression of thyroid hormone receptor-β1 mRNA in esophageal cancer

Abstract

Thyroid hormone receptors (TR), ligand-mediated transcription factors, regulate cell growth, differentiation, and apoptosis. In humans, two different genes encode TR-α and TR-β and they are often co-expressed in various tissues at different levels. To explore the role of TR in esophageal cancer, we analyzed expression of TR-β1 mRNA (most abundantly expressed in the majority of normal cells) in normal and malignant esophageal tissue specimens using in situ hybridization. The TR-β1 mRNA was detected in 92.3% (96 of 104) of normal esophageal mucosa, whereas TR-β1 mRNA was only detected in 55.8% (58 of 104 cases) of esophageal squamous cell carcinoma specimens (P<0.00001). Expression of TR-β1 mRNA was associated with well-differentiated cancers (P<0.001). Furthermore, we determined whether the loss of heterozygosity (LOH) in TR-β gene locus would be responsible for the lost TR-β1 expression. Analysis of 73 esophageal tissue specimens generated 39 informative cases, 17 of which showed LOH (43.6%) but only 9 of these 17 cases were correlated with lost TR-β1 expression. This study demonstrated that expression of TR-β1 mRNA was lost in esophageal cancer tissues, which may be due to multiple mechanisms.

Keywords

esophageal cancer / thyroid hormone receptor / in situ hybridization / LOH

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