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...
| Autores principales: | , , , , , , , |
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| Formato: | Artículo revista |
| Lenguaje: | Español |
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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: |
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I10-R327-article-26188 |
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| record_format |
ojs |
| institution |
Universidad Nacional de Córdoba |
| institution_str |
I-10 |
| repository_str |
R-327 |
| container_title_str |
Revista de la Facultad de Ciencias Médicas de Córdoba |
| language |
Español |
| format |
Artículo revista |
| topic |
pituitary senescence NF-kB estrogen receptor alpha tumour hipófisis senescencia NF-kB estrogenico alfa tumor |
| spellingShingle |
pituitary senescence NF-kB estrogen receptor alpha tumour hipófisis senescencia NF-kB estrogenico alfa tumor Mongi Bragato, B Grondona , E Sosa, LDV Zlocowski, N Petiti, JP Torres, A Gutierrez, S De Paul, AL Nuclear factor kappa B (NF-κB) and estrogen receptor alpha (ERα) interaction in the cellular senescence of experimental pituitary tumors |
| topic_facet |
pituitary senescence NF-kB estrogen receptor alpha tumour hipófisis senescencia NF-kB estrogenico alfa tumor |
| author |
Mongi Bragato, B Grondona , E Sosa, LDV Zlocowski, N Petiti, JP Torres, A Gutierrez, S De Paul, AL |
| author_facet |
Mongi Bragato, B Grondona , E Sosa, LDV Zlocowski, N Petiti, JP Torres, A Gutierrez, S De Paul, AL |
| author_sort |
Mongi Bragato, B |
| title |
Nuclear factor kappa B (NF-κB) and estrogen receptor alpha (ERα) interaction in the cellular senescence of experimental pituitary tumors |
| title_short |
Nuclear factor kappa B (NF-κB) and estrogen receptor alpha (ERα) interaction in the cellular senescence of experimental pituitary tumors |
| title_full |
Nuclear factor kappa B (NF-κB) and estrogen receptor alpha (ERα) interaction in the cellular senescence of experimental pituitary tumors |
| title_fullStr |
Nuclear factor kappa B (NF-κB) and estrogen receptor alpha (ERα) interaction in the cellular senescence of experimental pituitary tumors |
| title_full_unstemmed |
Nuclear factor kappa B (NF-κB) and estrogen receptor alpha (ERα) interaction in the cellular senescence of experimental pituitary tumors |
| title_sort |
nuclear factor kappa b (nf-κb) and estrogen receptor alpha (erα) interaction in the cellular senescence of experimental pituitary tumors |
| description |
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. |
| publisher |
Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología |
| publishDate |
2019 |
| url |
https://revistas.unc.edu.ar/index.php/med/article/view/26188 |
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I10-R327-article-261882024-08-27T18:26:54Z Nuclear factor kappa B (NF-κB) and estrogen receptor alpha (ERα) interaction in the cellular senescence of experimental pituitary tumors Interacción entre el factor nuclear kappa B (NF-kB) y el receptor estrogénico alfa (ERa) en la senescencia celular de tumores hipofisarios experimentales Mongi Bragato, B Grondona , E Sosa, LDV Zlocowski, N Petiti, JP Torres, A Gutierrez, S De Paul, AL pituitary senescence NF-kB estrogen receptor alpha tumour hipófisis senescencia NF-kB estrogenico alfa tumor 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. En investigaciones previas demostramos el surgimiento del proceso de senescencia celular prematura como un mecanismo de control del crecimiento celular durante la progresión tumoral hipofisaria inducida por estrógeno. Además, esta hormona ejerce una acción moduladora sobre la proliferación de células hipofisarias. Considerando el papel del factor de transcripción NF-κB, como moduilador la senescencia celular y tambiénde la progresión tumoral y la convergencia entre las vías de señalización receptor estrogénico alfa (ERα) y NF-kB en el control del ciclo celular, nos propusimos evaluar la asociación entre estas dos proteínas en tumores hipofisarios experimentales. El tumor hipofisario se indujo en ratas Wistar macho adultas mediante la implantación subcutánea de cápsulas de silástico conteniendo benzoato de estradiol (30 mg) durante 10, 20, 40 y 60 días (E10-60; n=5). El grupo control fue implantado con cápsulas vacía (n=5). Posteriormente, mediante inmunoprecipitación se evaluó la asociación entre ERα-NF-kB en las diferentes etapas del desarrollo tumoral. Además, se evaluaron los niveles de NF-kB e IkBα (inhibidor específico deNF-kB) en fracciones nucleares y citosólicas mediante Western Blot. La co-localización ERα: NF-kB se determinó mediante inmunofluorescencia (IF) y microscopía electrónica de transmisión (TEM). El análisis estadístico: ANOVA-Fischer (p<0,05). Durante el curso del desarrollo tumoral hipofisario inducido por estrógeno, se detectó una significativa asociación proteína-proteína ERα: NF-kB, con una marcada interacción en los estadios E10 y E60 de evolución tumoral, resultado que fue corroborado por IF y TEM. Además, se detectó un aumento significativo en los niveles proteicos de NF-kB e IkBα en el compartimento citosólico. Igualmente, se evidenció un aumento sustancial en los niveles nucleares de NF-kB en etapas intermedias del desarrollo tumoral (E20 y E40) en comparación con los observados en E10 y E60. Los resultados permiten concluir que existirá una asociación entre ERα y NF-kB a nivel citoplásmico a fin de inhibir su función como factor de transcripción y, por lo tanto, regular los mecanismos moleculares asociados a la senescencia y proliferación celular durante la progresión del tumor hipofisario experimental. Estos hallazgos permitiríabn exponer la existencia de un crosstalk entre la vía de señalización del NF-kB y la del ERα que contribuiría al control del crecimiento tumoral. Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2019-11-01 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion application/pdf https://revistas.unc.edu.ar/index.php/med/article/view/26188 Revista de la Facultad de Ciencias Médicas de Córdoba.; 2019: Suplemento JIC XX Revista de la Facultad de Ciencias Médicas de Córdoba; 2019: Suplemento JIC XX Revista da Faculdade de Ciências Médicas de Córdoba; 2019: Suplemento JIC XX 1853-0605 0014-6722 10.31053/1853.0605.v76.nSuplemento spa https://revistas.unc.edu.ar/index.php/med/article/view/26188/28006 Derechos de autor 2019 Universidad Nacional de Córdoba https://creativecommons.org/licenses/by-nc/4.0 |