The effect of T4 on mammary tumor cells depends on the interaction with ovarian steroids.

CANO R; ZYLA L; GOMEZ SE; PISTONE CREYDT V; LÓPEZ FONTANA C; CARÓN RW

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias; 2023

Sociedad Argentina de investigación Clínica (SAIC)

Hypothyroidism seems to be a protective factor against breast cancer (BCa) but long-term exposure or overdoses of thyroid replacement therapy with thyroxine (T4) may increase BCa risk. We previously observed that hypothyroidism prolonged the latency of appearance, reduced incidence, and retarded growth of tumors in rats, and that T4 regulated mammary carcinogenesis by interacting with other hormone pathways. In the present study, we analyzed the biological activity of T4, alone or combined with steroid hormones, on proliferation, viability, adhesion, and migration of human BCa cell lines. MCF-7 (REα+, REβ+, PgR+, TRβ1+) were treated with 10-9 M of T4; 17β estradiol (E2) and/or progesterone (P4), or DMEM/F12 with 1% FBSc as control. We evaluated proliferation and adhesion by MTT, viability by trypan blue and migration by wound healing. To verify if the biological effects were mediated by the genomic and/or non-genomic action of T4, the experiments were repeated using the TR inhibitor (1-850, Cayman Chemical, MI, USA). We evaluated the expression of proteins related to proliferation and apoptosis by western blot. Statistical analysis was performed using Student T test, ANOVA I and Bonferroni as post-test (p