Ação extra-nuclear do hormônio triiodotironina (T3) na expressão gênica de HIF-1α e TGFα em linhagem celular de adenocarcinoma mamário

• Autor(a) principal: Moretto, Fernanda Cristina Fontes [UNESP]
• Data de Publicação: 2015
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://hdl.handle.net/11449/131858
• topic: Hormonios tireoidianos; Mamas - Cancer; Expressão gênica; Adenocarcinoma; Thyroid hormones

In the literature it has been demonstrated that high levels of expression of HIF-1α in human BC are related to mammary carcinogenesis and molecular changes resulting from the tumor vascularization process. In previous work from our group, we showed that the TGFα expression is increased upon treatments with T3, but this increase does not occur in cellular models devoid of the estrogen receptor or when the cells are concomitantly treated with the antiestrogen compound Tamoxifen. The objective of this study is to determine the extranuclear action of T3 hormone on HIF-1α and TGFα expression in MCF7 breast adenocarcinoma cell line. The cells were subjected to treatment with 10-8M T3 for 10', 30', 1h and 4h in the presence or absence of inhibitors Fulvestrant- ER inhibitor-, Actinomycin D - gene expression inhibitor -, cyclohexamide - protein synthesis inhibitor-, and LY294002 - PI3K inhibitor. The HIF-1α and TGFα mRNA expressions were analyzed by RT-PCR. For data analysis we used ANOVA complemented with Tukey test and adopted minimum 5% significance. The present study confirms that the gene expressions of HIF-1α and TGFα are increased in the presence of T3 in MCF-7 cells at all times studied. T3 represses HIF-1α at all time points assessed after inhibition of transcription, though for TGFα this effect was observed only at 10', after what no significant difference in its expression was detected, with inhibition of transcription. Furthermore, we suggest that the action of T3 on the expression of these genes occurs indirectly and occurs through activation of PI3K pathway, in the cell line studied