| Grant number: | 14/15209-5 |
| Support Opportunities: | 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 Investigator: | Celia Regina Nogueira |
| Grantee: | Fernanda Cristina Fontes Moretto |
| 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 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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