RESUMO
Breast cancer is the most frequent neoplasia in developed countries and the leading cause of death in women worldwide. Epithelial-to-mesenchymal transition (EMT) is a cellular process through which epithelial cells decrease or lose their epithelial characteristics and gain mesenchymal properties. EMT mediates tumor progression, because tumor cells acquire the capacity to execute the multiple steps of invasion and metastasis. Benzo[a]pyrene (B[a]P) is an environmental organic pollutant generated during the burning of fossil fuels, wood, and other organic materials. B[a]P exposition increases the incidence of breast cancer, and induces migration and/or invasion in MDA-MB-231 and MCF-7 breast cancer cells. However, the role of B[a]P in the induction of an EMT process and metastasis of mammary carcinoma cells has not been studied in detail. In this study, we demonstrate that B[a]P induces an EMT process in MCF10A mammary non-tumorigenic epithelial cells. In addition, B[a]P promotes the formation of larger tumors in Balb/cJ mice inoculated with 4T1 cells than in untreated mice and treated with dimethyl sulfoxide (DMSO). B[a]P also increases the number of mice with metastasis to brain and the total number of brain metastatic nodules in Balb/cJ mice inoculated with 4T1 cells compared with untreated mice and treated with DMSO. In conclusion, B[a]P induces an EMT process in MCF10A cells and the growth of mammary tumors and metastasis to brain in Balb/cJ mice inoculated with 4T1 cells.
Assuntos
Benzo(a)pireno , Neoplasias Encefálicas , Transição Epitelial-Mesenquimal , Camundongos Endogâmicos BALB C , Animais , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Benzo(a)pireno/toxicidade , Humanos , Camundongos , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/induzido quimicamente , Neoplasias da Mama/patologia , Neoplasias da Mama/induzido quimicamente , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacosRESUMO
Bisphenol A (BPA) is an industrial synthetic chemical used in the production of polycarbonate plastics and epoxy resins. Human exposition to BPA is primarily through eating food, and drinking liquids, because BPA can leach from polycarbonate plastic containers, beverage cans and epoxy resins. BPA induces proliferation and migration in human breast cancer cells. The G protein-coupled estrogen receptor (GPER) is a G protein-coupled receptor coupled with Gs proteins that is activated by estrogen and estrogenic compounds and it is the receptor for BPA. However, the signal transduction pathways that mediate migration via BPA/GPER in triple negative breast cancer (TNBC) cells has not been studied in detail. Here, we demonstrate that BPA induces an increase of GPER expression and activation of FAK, Src and ERK2, and an increase of focal adhesion assembly via GPER in TNBC MDA-MB-231 cells. Moreover, BPA induces FAK and ERK2 activation, focal adhesion assembly and migration via epidermal growth factor receptor (EGFR) transactivation. Collectively our data showed that BPA via GPER and/or EGFR transactivation induces activation of signal transduction pathways that mediate migration in TNBC MDA-MB-231 cells.