Alterations of thyroid hormone receptor α gene: frequency and association with Nm23 protein expression and metastasis in gastric cancer

Thyroid hormone receptor genes (c-erbA, or TR) have been implicated as tumor suppressor genes. We investigated whether two subtypes of TR genes (TRα and TRβ) are altered in human gastric cancer, as well as the role of such alterations in tumor metastasis. As a preliminary survey (n=18), Southern blot analysis was conducted with full-length TRα or TRβ cDNA probes, after digestion with restriction enzyme (EcoRI, BamHI, or HindIII). The survey showed the most frequent alteration was in TRα gene by a loss of two HindIII fragments (7.1 and 10.1 kb). Subsequent study focused at this TRα alteration by increasing patient number up to a total of 42. TRα alteration was noted in 19 (49%) of the 39 patients with informative results. The TRα alteration was associated with the development of distant (hematogenous) metastasis (P=0.0084) and high expression level of Nm23 protein (P=0.020). These findings suggest that TRα might be involved in tumorigenesis, and that interactions between the TRα and nm23 genes might take part in hematogenous metastasis of gastric cancer.