GPER1 activation by estrogenic compounds in the inflammatory profile of breast cancer cells
Por:
Mariana S.-M., Brenda R.-P., Heriberto P.-G., Cristina L., David B., Guadalupe Á.-L.
Publicada:
1 ene 2025
Ahead of Print:
1 nov 2024
Resumen:
Breast cancer (BC) is the most frequent female neoplasm worldwide. Its establishment and development have been related to inflammatory cytokine expression. Steroid hormones such as estradiol (E2) can regulate proinflammatory cytokine secretion through interaction with its nuclear receptors. However, little is known regarding the activation of its membrane estrogen receptor (GPER1) and the inflammatory cytokine environment in BC. We have studied the synthesis and biological effects of molecules analogs to E2 for hormone replacement therapy (HRT), such as pentolame. Nevertheless, its interaction with GPER1 and the modulation of inflammatory cytokines in different BC types has been barely studied and deserves deeper investigation. In this research, the role of GPER1 in the proliferation and modulation of inflammatory cytokines involved in carcinogenesis and metastatic processes in different BC cell lines was assessed by binding to various compounds. To achieve this goal, the presence of GPER1 was identified in different BC cell lines. Subsequently, cell proliferation after exposure to E2, pentolame and GPER1 agonist, G1, was subsequently determined alone or in combination with the GPER1 antagonist, G15. Finally, the pro-inflammatory cytokine secretion derived from the supernatants of BC cells exposed to the previous treatments was also assessed. Interestingly, GPER1 activation or inhibition has significant effects on the cytokine regulation associated with invasion in BC. Notably, pentolame did not induce cell proliferation or increase the proinflammatory cytokine expression compared to E2 in BC cell lines. In addition, pentolame did not induce the presence of the cell adhesion molecule PECAM-1. In contrast, E2 treatment weakly induced the expression of PECAM-1 in MCF-7 and HCC1937 cells, and G1 treatment showed this effect only in MCF-7 cells. The results suggest that GPER1 might be a significant inflammatory modulator with angiogenic-related effects in BC cells. In addition, pentolame might represent an HRT alternative in patients with BC predisposition. © 2024
Filiaciones:
Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de Mexico, Mexico
Facultad de Estudios Superiores Zaragoza. Universidad Nacional Autónoma de México, Ciudad de México, Mexico
Laboratorio de Onco-Inmunobiología, Departamento de Enfermedades Crónico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias, “Ismael Cosio Villegas” Calzada de Tlalpan 4502, Col. Sección XVI, Ciudad de México, 14080, Mexico
Departamento de Biología de la Reproducción “Dr. Carlos Gual Castro”, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Av. Vasco de Quiroga No. 15, Col. Belisario Domínguez, Sección XVI, Ciudad de México, 14080, Mexico
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