Thyroid hormone regulation of mammary adenocarcinoma cells

VALLI E; BARREIRO ARCOS ML; CRICCO G; CREMASCHI G; MARTÍN G

Ciudad Autónoma de Buenos Aires

Congreso; XXXIX Reunión Anual de la Sociedad Argentina de Farmacología Experimental; 2007

SAFE

Thyroid hormones (TH) exert a broad range of effects on development, growth and metabolism. Their actions on lymphoid cell growth were recently analyzed and we have described that both 3,5,3’-L-triiodothyronine (T3) and thyroxine (T4) are able to increase T lymphoma cell proliferation through the increment of both nitric oxide synthase (NOS) activity as well as of its inducible isoform expression at the protein and mRNA levels. To further characterize TH actions on other tumor cells, the aim of this work was to study their effects on the mammary adenocarcinoma cell line MDA MB231 (MDA). Through cell count by clonogenic assay and by carboxyfluorescein diacetate succinimidyl ester (CFSE) labeling, dose response curves for both T3 and T4 actions upon cell division were performed. We found a dual action of TH on MDA cell growth, with physiologic concentrations of TH leading to inhibition, while lower concentrations stimulating cellular growth. To further analyze NOS participation at any of these doses, NOS activity was evaluated by conversion of [14C]-Arginine to radiolabeled citruline. No modification of NOS activity was observed. TH were also able to regulate metalloproteinase levels in MDA cells. From these results it can be concluded that TH are able to modulate mammary tumor cell growth as occur in lymphoma cells, but with no involment of NOS activity and affecting angiogenic factor production.