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-231, MDA-MB-468, and T-47D and ovarian cancer cell line OVCAR-3 to test the response to cell proliferation.


METHODS
Breast and ovarian cancer cell lines were placed in serum-free medium prior to addition of effector. Proliferation was determined by thymidine incorporation. For Northern analysis, RNA was isolated and c-fos, cjun and TIEG expression assessed.


RESULTS
No compound provided uniform results across all cell lines. T2 inhibited 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 proliferation in all cell lines except T-47D in which two-state behavior occurred, with increased proliferation at low concentrations (< or = 10(-6) M) and decreased proliferation at high concentrations (> or = 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 proliferation 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 OVCAR-3 cells. Protooncogene expression was increased by both transferrin and T4 in the cell lines tested.


CONCLUSIONS
Correlation of iodines and proliferative responses were used to determine "essential" iodines necessary to produce the observed effect. Interaction between these cancer cells and non-physiological concentrations of thyroid hormone can be explained by thyroid hormone receptors with altered binding properties. Thus, interaction of thyroid hormones and cancer cells may differ from what occurs with normal cells.
Martinez
M B
MB
Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA.
Ruan
M
M
Fitzpatrick
L A
LA
D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D004104:Diiodothyronines / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*; D016760:Proto-Oncogene Proteins c-fos / Q000494:pharmacology; D013963:Thyroid Hormones / Q000494:pharmacology*; D013974:Thyroxine / Q000494:pharmacology; D014168:Transferrin / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology; D014285:Triiodothyronine, Reverse / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004104:Diiodothyronines; D016760:Proto-Oncogene Proteins c-fos; D013963:Thyroid Hormones; D014168:Transferrin; D014284:Triiodothyronine; C030103:3,5-diiodothyronine; D014285:Triiodothyronine, Reverse; D013974:Thyroxine