Dados do Resumo

Título

Polychlorinated biphenyls disrupt epithelial-mesenchymal transition gene expression and MAPK signaling pathway in human thyroid tumor cells

Introdução

The use of polychlorinated Biphenyls (PCBs) was banned in industry more than 25 years ago, since they are persistent contaminants in the environment. Studies have demonstrated that PCBs act as thyroid disruptors, altering serum concentrations of T3, T4 and TSH in humans and rodents. Previous studies of our group have demonstrated that PCBs disrupt thyroid gene expression through epigenetic mechanisms and dysregulation of PKA and MAPK signaling pathways.

Objetivo

This study aimed to evaluate the effects of PCBs exposure on thyroid signaling pathways and the epithelial-mesenchymal transition gene expression in normal and tumor human thyroid cells.

Métodos

Nthy-ori 3-1 (Normal Human Thyroid Follicular Epithelial Cell), B-CPAP and TPC-1 (Human Papillary Thyroid Carcinoma) cell lines were cultured and subsequently treated or not (control) for 24 hours with a nanomolar dose (10-9 M) of Aroclor 1254, a known mixture of PCBs. The expression of genes involved in the epithelial-mesenchymal transition (Snail, Twist and E-cadherin) was evaluated by RT-PCR and PKA and MAPK signaling pathways was evaluated by Western Blotting.

Resultados

The treatment of thyroid tumor cells with PCBs reduced the expression of mesenchymal markers, such as TWIST and SNAIL, compared to the control group, especially in the TPC1 cell line. There was no significant difference in E-cadherin expression between cells treated or not treated with Aroclor. Interestingly, the TPC1 cell line showed a reduction in ERK signaling pathway activation after treatment with PCBs. The other cell lines did not show significant changes in the activation of the studied signaling pathways.

Conclusões

The treatment with PCBs reduced the expression of mesenchymal markers in thyroid tumor cells, as well as the signaling of the MAPK pathway, especially in the TPC1 cell line. Future studies will be necessary to clarify the regulatory mechanisms and the functional consequences of the mesenchymal gene expression pattern in these cells.

Financiador do resumo

FAPESP (2024/09279-2)

Palavras Chave

Polychlorinated biphenyls; Epithelial-mesenchymal transition; Thyroid Cancer