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Indirect gene expression activation by triiodothyronine in breast cancer cell lines

Grant number: 15/21575-7
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): January 01, 2016
Effective date (End): December 31, 2016
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Sandro José Conde
Grantee:Beatriz Caroline de Moraes
Home Institution: Instituto Federal de Educação, Ciência e Tecnologia de São Paulo (IFSP). Campus São Roque. São Roque , SP, Brazil

Abstract

It is known that the patient's hormone status is important for proliferation and treatment of breast cancer (CaM). As for the thyroid hormone (T3), despite the contradictory epidemiological studies regarding its influence on breast cancer, laboratory studies have demonstrated its ability to increase proliferation of cells with CaM of E2 receptor (ER) positive. Although T3 exert many actions by the classical genomic regulation of gene transcription, there are genomic actions of thyroid hormones described in the plasma membrane, the cytoplasm and cell organelles. Recently it was shown that some genes (AREG, FBLN1, CLDN6, TGFA) were stimulated by T3 in MCF-7 cells, including the thyroid hormone receptor - alpha. It is intended to elucidate better the biochemical pathway of thyroid hormones in gene activation of these targets in cell lines of breast adenocarcinoma. Methodology: MCF-7 breast cancer cell lines are plated in intervals of 10-minute, 30 minutes, 1 hour and 48 hours with cycloheximide (50 mM), T3 (10-8M) and T3 (10-8M) + cycloheximide (50 mM). The treatments will be performed in triplicate and with a control treatment. After the treatments, will be held the quantification of gene expression THRA (thyroid hormone receptor - alpha), a gene with gene expression altered both in primary tumors and in cell lines of breast adenocarcinoma.Therefore, at the end, we will be able to determine whether the action of triiodothyronine on the gene expression of one of its receptors is caused directly or indirectly (depending on prior protein synthesis) in cell lines of breast cancer.