THYROXINE INDUCES THE PROLIFERATION OF MCF-7 CELLS VIA GENOMIC PATHWAYS

CANO, ROCÍO; FERRANDO, MATÍAS; ZYLA, LEILA; GÓMEZ, SILVINA; PISTONE-CREYDT, VIRGINIA; LÓPEZ- FONTANA, CONSTANZA; CARÓN, RUBÉN

San Juan

Congreso; XLI Reunión de la Sociedad de Biología de Cuyo; 2023

Sociedad de Biología de Cuyo

Hypothyroidism is considered a protective factor against breast cancer (BC). However, prolonged exposure to or excessive doses of thyroxine (T4) in thyroid replacement therapy may potentially elevate BC risk. The contribution of thyroid hormones (HT) to BC can be attributed to their genomic and non-genomic effects. Genomic mechanisms entail T4 binding to intranuclear thyroid receptors (TRα or TRβ1), which, in turn, regulate the transcription of numerous genes. Non-genomic mechanisms involve T4 binding to plasma membrane receptors, including αVβ3 integrins, as well as cytoplasmic TRβ1 or TRα. These interactions activate pathways such as ERK and AKT/PI3K, ultimately promoting cell proliferation. In this study, our objective was to investigate the biological impact of T4 on MCF-7 breast tumor cells and examine its potential genomic and non-genomic effects. To achieve this, we utilized a final concentration of 10-9 M of T4, administered both alone and in combination with a TR inhibitor (1-850, Cayman Chemical, MI, USA), in a culture medium of DMEM/F12 with phenol red and 1% charcoalized fetal serum (FBSc) for 24 h (genomic effects) and 20-minute (non-genomic effects). We assessed cell proliferation via MTT assays, and cell viability using Trypan Blue, and explored genomic and non-genomic pathways through western blot analysis. After 24 h of T4 treatment, we observed that T4 enhanced cell proliferation and increased MCF-7 cell viability. However, the addition of 1-850 reduced their viability. Moreover, T4 exhibited a tendency to suppress apoptotic processes, as indicated by reduced expression of caspases (3, 7, and 8) and the Bax/BCL-xL ratio. Meanwhile, a 20-minute T4 treatment activated the pERK/ERK pathway. In conclusion, T4 primarily exerts its proliferative effects on hormone-sensitive mammary tumor cells through genomic pathways.