Determination of er± and ER² receptor participation in the action of triiodotironine (T3) in modulation of PR gene expression in MCF-7 breast adenocarcinoma cells

• Grant number: 17/10059-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2018
• End date: October 31, 2019
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Celia Regina Nogueira
• Grantee: Larissa Silva Dall Aqua
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated research grant: 13/05629-4 - Genomic vs nongenomic actions of thyroid hormones: changes of paradigms, physiological implications and therapeutical perspectives, AP.TEM

Abstract

Breast cancer (BC) is one of the highest incidences among women and the highest mortality. Among BC variants, there are dependent hormones, in which estrogen (E2) on the estrogen receptor (ER) is well established in relation to BC progression. Although controversial, clinical studies show that there is a worse prognosis of BC when associated with thyroid pathology, especially hyperthyroidism. Experimental studies more clearly demonstrate the association of hyperthyroidism and BC. This probably occurs because, at high doses, triiodothyronine (T3) is able to bind to the estrogen receptor and produce E2-like effects. As an example, one has the induction of expression of genes normally modulated by E2, such as the progesterone receptor (PR) gene. As the induction of PR by E2 is well established, and there is an induction of similar genetic expression by T3 and E2 stimulus, it is important to evaluate the modulation of PR by T3. The objective of this work is to verify the action of T3 on the progesterone receptor (PR) genetic expression in MCF-7 breast adenocarcinoma cells with ER silencing. Incubation of the cells will be performed and they will be submitted to ER silencing and subsequent treatment at the supraphysiological dose of T3 (10-8M) for one hour. After the treatment period, the analysis of gene expression of PR mRNA by RT-PCR will be performed. The hypothesis is that in promoting ER± and ER² silencing in MCF-7 cells, there is a decrease in T3-induced PR genetic expression.