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Extranuclear actions of triiodothyronine and estrogen on breast cancer cell lines

Grant number: 12/04684-9
Support type:Regular Research Grants
Duration: July 01, 2012 - December 31, 2014
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Celia Regina Nogueira
Grantee:Celia Regina Nogueira
Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

It is known that estrogen (E2) and the hormonal status of the patient are important for the proliferation and treatment of breast cancer (CaM). As for the thyroid hormone (T3), although epidemiological studies are still contradictory about its influence on breast cancer, laboratory studies have demonstrated its ability to increase proliferation of cells with CaM E2 receptor (ER) positive, inducing expression of genes normally stimulated by E2 (PR, TGFa). Although T3 exert many actions by the classical genomic regulation of gene transcription, a number of effects of T3 occurs rapidly and are not affected by inhibitors of protein synthesis. Non-genomic actions of thyroid hormones are described in the plasma membrane, cytoplasm and cell organelles. In vitro, independent of protein synthesis, thyroxine (T4) induced inositol triphosphate (IP3) and calcium signaling by increasing the effects of interferon-g by PKC and PKA. Recently our group demonstrated that the gene Amphiregulin (AREG) and TGFA was stimulated by E2 and T3 in MCF-7 cells; while HIF1A has upregulation by T3 treatment with direct non-genomic pathway. Thus, our hypothesis is that thyroid hormone alters the AREG, TGFA and HIF1A gene expression without binding to nuclear receptors, via the activation of PI3K. We intend to elucidate the route of action of thyroid hormones in the activation of the amphiregulin gene in cell lines of breast adenocarcinoma. Methodology: The cell line of breast cancer MCF-7 and MDA will be tagged at intervals of 10 minutes, 30 minutes, 1 hour and 4 hours with E2 (10-7M), T3 (10-8M), E2 (10-7M) + ICI (1µM), T3 (10-8M) + ICI (1µM), ICI (1µM) in the absence or presence of actinomycin, cycloheximide or LY294002. It will be held extraction of total RNA to obtain cDNA - Reverse transcription (RT) of RNA and real-time PCR for the expression of AREG, TGFA and HIF1A in each treatment. Western blot airway MAPKs (ERK1/ERK2 and p38). (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FONTES MORETTO, FERNANDA CRISTINA; DE SIBIO, MARIA TERESA; LUVIZON, ALINE CARBONERA; CASTRO OLIMPIO, REGIANE MARQUES; DE OLIVEIRA, MIRIANE; BARNABE ALVES, CARLOS AUGUSTO; CONDE, SANDRO JOSE; NOGUEIRA, CELIA REGINA. Triiodothyronine (T-3) induces HIF1A and TGFA expression in MCF7 cells by activating PI3K. Life Sciences, v. 154, p. 52-57, JUN 1 2016. Web of Science Citations: 3.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.