Nuclear factor kappa B (NF-κB) and estrogen receptor alpha (ERα) interaction in the cellular senescence of experimental pituitary tumors
In previous investigations we demonstrated the emergence of premature cellular senescence process as a mechanism of cell growth control during estrogen-induced pituitary tumoral progression. In addition, it is known that this hormone exerts a modulating action on pituitary cell proliferation. Consid...
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| Autores principales: | , , , , , , , |
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| Formato: | Artículo revista |
| Lenguaje: | Español |
| Publicado: |
Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
2019
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| Materias: | |
| Acceso en línea: | https://revistas.unc.edu.ar/index.php/med/article/view/26188 |
| Aporte de: |
| Sumario: | In previous investigations we demonstrated the emergence of premature cellular senescence process as a mechanism of cell growth control during estrogen-induced pituitary tumoral progression. In addition, it is known that this hormone exerts a modulating action on pituitary cell proliferation. Considering the role of the NF-κB transcription factor, as a modulator of cell senescence, and also of tumoral progression, and the convergence between estrogen receptor alpha (ERα) and NF-κB signaling pathways in the control of cell cycle, we proposed to evaluate the association between these two proteins in experimental pituitary tumors.
The pituitary tumour was induced in adult male Wistar rats by subcutaneous implantation of silastic capsules containing estradiol benzoate (30 mg) for 10, 20, 40 and 60 days (E10-60; n=5). The control group was implanted with empty capsules (n=5). Subsequently, the ERα and NF-κB association, along the different stages of tumor development, was evaluated by immunoprecipitation. In addition, of NF-κB and IκBα protein levels from nuclear and cytosolic fractions were evaluated by Western Blot. ERα: NF-κB co-localization was determined by immunofluorescence (IF) and transmission electron microscopy (TEM). Statistical analysis of the data was performed using ANOVA-Fischer (p<0.05).
During the course of estrogen-induced pituitary tumour development, a significant protein-protein ERα: NF-κB association was detected, with a marked interaction at E10 and E60 stages of tumor evolution, data also corroborated by IF and TEM. In addition, a significant increase in NF-κB and IκBα protein levels was detected in the cytosolic compartment. Likewise, there was a substantial increase in NF-κB nuclear levels at intermediate stages of tumor development (E20 and E40) compared to those observed in E10 and E60.
The results allow us to conclude that ERα would recruit NF-κB at the cytoplasmic level in order to inhibit its function as a transcription factor and, therefore, to modulate the molecular mechanisms associated with senescence and cell proliferation during the progression of the experimental pituitary tumor. These findings suggest the existence of a crosstalk between the NF-κB and ERα signaling pathways that would contribute to tumoral growth control. |
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