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PARTICIPATION OF T3 IN POST-TRANSCRIPTIONAL CONTROL OF HIF-1± AND TGF± EXPRESSION IN CELL LINES OF BREAST CANCER AND EVALUATION OF THE INVOLVEMENT OF POTENTIAL miRNAS

Grant number: 14/15209-5
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2015
Effective date (End): February 28, 2019
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal researcher:Celia Regina Nogueira
Grantee:Fernanda Cristina Fontes Moretto
Home 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

Several environmental risk factors, pathological conditions and physiological agents such as thyroid hormones (TH), have been proposed by induce the influence the development of breast cancer (BC). Our group showed the action of Triiodothyronine (T3) on different genes in breast cancer cells lines using microarray and the action of genes were studied Hypoxia-inducible factor-1 alpha (HIF-1±) and Transforming growth factor alpha (TGF±), but this study did not evaluate the mechanism of action by which T3 regulates the expression of these genes and their involvement in extranuclear pathway. Subsequently, the master degree of the candidate in question, we approach nuclear and extranuclear action of T3 on gene expression of HIF-1± and TGF± genes in the MCF-7 breast cancer cell lines. Our work demonstrated that the gene expression of HIF-1± and TGF± increased in patients T3, in strains of breast cancer, and it was observed that the activation of PI3K by T3 is required for modulation of HIF-1± and TGF± genes. These findings lead us to further investigations to elucidate the pathways of T3 actions, by the use of specific drugs to block intracellular signaling pathways to approach TH non-genomic actions, such as PD98059 (ERK/MAPK inhibitor) and RGD peptide (which binds to ±v²3 integrin; initiation site of various actions of thyroid hormones and their analogues in the cell membrane). The treatments cited before will be performed in culture of breast cancer cell lines (MCF-7), incubate with T3 in the presence and absence of these drugs, with subsequent analysis of gene expression (RT-PCR) and protein expression (Western blot) of HIF-1± and TGF± gene. We will also investigate the participation of microRNAs involved in breast cancer, such as miR let-7a, miR-200a and miR-335, in the events triggered by TH, analyzing their expression by RT-PCR.

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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)
TABATA M. SILVA; FERNANDA C. F. MORETTO; MARIA T. DE SIBIO; BIANCA M. GONÇALVES; MIRIANE OLIVEIRA; REGIANE M. C. OLIMPIO; DIEGO A. M. OLIVEIRA; SARAH M. B. COSTA; IGOR C. DEPRÁ; VICKELINE NAMBA; et al. Triiodothyronine (T3) upregulates the expression of proto-oncogene TGFA independent of MAPK/ERK pathway activation in the human breast adenocarcinoma cell line, MCF7. ARCHIVES OF ENDOCRINOLOGY METABOLISM, v. 63, n. 2, p. 142-147, . (13/05629-4, 14/15209-5, 15/09686-8)
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, . (12/04684-9, 14/15209-5)
SILVA, TABATA M.; MORETTO, FERNANDA C. F.; DE SIBIO, MARIA T.; GONCALVES, BIANCA M.; OLIVEIRA, MIRIANE; OLIMPIO, REGIANE M. C.; OLIVEIRA, DIEGO A. M.; COSTA, SARAH M. B.; DEPRA, IGOR C.; NAMBA, VICKELINE; et al. Triiodothyronine (T-3) upregulates the expression of proto-oncogene TGFA independent of MAPK/ERK pathway activation in the human breast adenocarcinoma cell line, MCF7. ARCHIVES OF ENDOCRINOLOGY METABOLISM, v. 63, n. 2, p. 142-147, . (15/09686-8, 14/15209-5, 13/05629-4)

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