Increased invasive activity of human hepatocellular carcinoma cells is associated with an overexpression of thyroid hormone β1 nuclear receptor and low expression of the anti-metastatic nm23 gene

To understand the role of thyroid hormone in metastasis, we studied the expression of the anti-metastatic nm23 gene in eight human hepatocellular carcinoma (HCC) cell lines. These cells differentially expressed the anti-metastatic nm23 gene. A low level of nm23 proteins was found to have a high in vitro invasive activity which correlated closely with an overexpression of the thyroid hormone β1 nuclear receptor (h-TRβ1). Concurrent with the down-regulation of h-TRβ1, the invasive activity of HCC cells was suppressed by the thyroid hormone, 3,3′,5-triiodo-l-thyronine (T₃). These results indicate that the invasive activity of HCC cells was regulated by T₃, suggesting that T₃ could be involved in modulating the functions of nm23.