IN VITRO EFFECTS OF T4 ON APOPTOSIS AND PROLIFERATION OF MAMMARY TUMORS

SASSO, CORINA V.; BRUNA, FLAVIA; SANTIANO, FLAVIA E.; ZYLA, LEILA E; GÓMEZ, SILVINA E; PISTONE CREYDT, VIRGINIA; LOPEZ-FONTANA, CONSTANZA M.; CARÓN, RUBÉN W.

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Ouraim was to study the genomic effects produced by thyroid hormones (TH) onmammary tumors from hypo-, eu- and hyperthyroid rats. Female Sprague‑Dawleyrats were treated with a single dose of dimethylbenzathracene (15 mg/rat) at 55days of age, and were divided into three groups: hypothyroidism (HypoT; 0.01%6-N-propyl-2-thiouracil in drinking water, n=10), hyperthyroidism (Hyper,0.25mg / kg / day Tyroxine -T4- via sc; n=10) and EUT (untreatedcontrol, n=10). At sacrifice, tumor explants were obtained and treated with 10-10 M T4 and/or 10-9 M 17β-estradiol (E2) inDMEM/F12 without phenol red with 1% Charcoalized Fetal Bovine Serum (SFBc) for24 h to evaluate changes in the expression of hormone receptors and proteinsrelated to apoptosis and proliferation by immunohistochemistry and WesternBlot. Statistical analysis was performed using ANOVA I and Bonferroni?s test aspost hoc. Administration of T4, E2 and T4+E2induced a significant increase in KI67 expression in all tumors. Only T4stimulation decreased total and cleaved caspase 3 and PARP expression in HypoTtumors while a slight increase of both apoptotic markers was observed in theHyper tumors. No significant apoptotic changes were observed in the tumors ofEUT. Regarding hormone receptors, administration of T4 increasedcytoplasmic progesterone receptor (PgR), nuclear expression of thyroid hormonereceptor β (TRβ) and favored the translocation to the nucleus of estrogenreceptor (RE) β in HypoT tumors. T4 enhanced the nuclear andcytoplasmic expression of REα and REβ in Hyper tumors. T4 and T4+E2augmented the expression of REα and PgR in EUT. E2 did notsignificantly modify the expression of hormone receptors. In conclusion, theadministration of T4 induced a differential expression of hormonereceptors according to the thyroid state of the tumor. It has a proliferativeeffect on all mammary tumors independent of the thyroid state but it onlyshowed an antiapoptotic role in Hypot tumors.