Nuclear thyroid hormone receptors in human cancer tissues

Abstract

Saturable, high affinity binding sites for 3,5,3' triiodothyronine (T3) were identified in nuclei isolated from human tumors of various origins (breast cancers, other epitheliomas, sarcomas, tumors of the central nervous system). Nuclear T3 receptors were present in all samples of primary breast cancer (n = 93; average Cmax = 215 fmol/mg DNA) and in metastatic tissues originating from breast tumors. A significantly lower T3 binding capacity was found in non-tumor tissues, obtained from breast sites distal to the tumor (n = 30; average Cmax = 133 fmol/mg DNA; paired t-test: p less than 0.01). Specific nuclear T3 receptors were also present in other epitheliomas (n = 8; average Cmax = 432 fmol/mg DNA), sarcomas (n = 4; average Cmax = 297 fmol/mg DNA) and cerebral tumors (n = 13; average Cmax = 364 fmol/mg DNA. In 93 cases of breast cancer, a negative relationship was found between the nuclear T3 receptor level and the involvement of axillary lymph nodes (Pearson chi square value: p = 0.017). Except a possible relationship between the T3 receptor and the progesterone receptor concentrations, no significant correlation was observed between the nuclear T3 binding capacity in breast cancer samples and other clinical and biochemical parameters: age, tumour stage, histopathological grade, serum concentrations of thyroid hormones, TSH, CEA (carcinoembryonic antigen) and prolactin, cytoplasmic estrogen receptors. The presence of high affinity T3-binding sites in human tumor nuclei indicates that the thyroid hormones may play a role, at the cellular level, on the development of certain human cancers.