Altered response to thyroid hormones by breast and ovarian cancer cells

Background In this study, L-thyroxine (T4), 3',3,5-triiodo-L-thyronine (T3) , 3,5-diiodo-L-thyronine (T2), reverse T3; 3',5',3-triiodo-L-thyronine (RT3 ) and transferrin were added to breast cancer cell lines Hs 578T, MDA-MB-23 1, MDA-MB-468 and T-47D and ovarian cancer cell line OVCAR-3 to test the re sponse to cell proliferation. Materials and Methods. Breast and ovarian can cel cell lines were placed in serum-free medium prior to addition of effect or: Proliferation was determined by thymidine incorporation. For Nar them a nalysis, RNA was isolated and c-fos, cjun and TIEG expression assessed Resu lts. No compound provided uniform results across all cell lines. T2 inhibit ed proliferation in Hs 578T and MDA-MB-468, had no effect in MDA-MB-231 and OVCAR-3, and stimulated proliferation in T-47D cells. T3 inhibited prolife ration in all cell lines except T-47D in which two-state behavior occurred, with increased proliferation at low concentrations (less than or equal to 10(-6) M) and decreased proliferation at high concentrations (greater than or equal to 10(-5) M). RT3 inhibited proliferation in Hs 578T; MDA-MB-231, and T-47D but had no effect in MDA-MB-468 and OVCAR-3. T4 inhibited prolife ration in Hs 578T, MDA-MB-231, and MDA-MB-468 and had two-state behavior in T-47D and OVCAR-3. Finally, transferrin increased proliferation only in OV CAR3 cells. Protooncogene expression was increased by both transferrin and T4 in the cell lines tested. Conclusions. Correlation of iodines and prolif erative responses were used to determine "essential" iodines necessary to p roduce the observed effect Interaction between these cancer cells and non-p hysiological concentrations of thyroid hormone can be explained by thyroid hormone receptors with altered binding properties. Thus, interaction of thy roid hormones and cancer cells may differ from what occurs with normal cell s.