Altered response to thyroid hormones by prostate and breast cancer cells

Transferrin, an abundant bone marrow constituent, has been shown to be a po tent mitogen in vitro in the prostate cancer cell line PC3. T4 (L-thyroxine ) and T3 (3',3,5-tri-iodo-L-thyronine) are regulators of cell metabolism. I n this study, the effects of nonphysiological concentrations (about two ord ers of magnitude higher) of T4, T3, T2 (3,5-di-iodo-L-thyronine), RT3 (reve rse T3, 3',5',3-tri-iodo-L-thyronine) and transferrin (about three orders o f magnitude lower) were tested on the prostate cancer cell lines PC3, DU145 and LNCaP, and the breast cancer cell line MCF-7. In PC3 cells, increased proliferation by transferrin could be reversed by the addition of T3 or T4. T4 decreased proliferation in all cell lines tested, while transferrin inc reased proliferation in PC3 cells only. T3 decreased proliferation in PC3, LNCaP and MCF-7 cells but had no effect on DU145 cells. T4 and T3 gave two- state behavior in LNCaP cells. These results were combined to determine the essential iodines which produced the observed proliferative effects. Cell lines responded differently to T4, T3, T2, RT3 and transferrin suggesting a specific interaction among the compounds tested and the different cell lin es. Finally, regulation of gene expression was demonstrated using DU145 cel ls. Upregulation of c-fos mRNA was observed in cultures at early time-point s in the presence of T4, transferrin or both. Decreased expression was obse rved at later time-points with no expression at 4 h. An explanation for the se results may be a change in thyroid hormone receptor/ligand affinity. Thu s, the interactions between thyroid hormones and cancer cells may be differ ent from those between thyroid hormones and normal cells.