EZH2 as a regulator of cell proliferation in pituitary tumors
Abstract: Pituitary adenomas are the most frequent intracranial neoplasms mainly benign in nature. However, they can occasionally lead to malignant endocrinopathies. Epigenetic modifications are described among the various factors proposed as guidelines for pituitary tumorigenesis. EZ...
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| Formato: | Artículo revista |
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Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
2021
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| Acceso en línea: | https://revistas.unc.edu.ar/index.php/med/article/view/34913 |
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I10-R327-article-34913 |
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Universidad Nacional de Córdoba |
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I-10 |
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R-327 |
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Revista de la Facultad de Ciencias Médicas de Córdoba |
| format |
Artículo revista |
| topic |
EZH2 proliferation 1schafer heidi, 2maggi ana luz Pituitary adenoma EZH2 proliferación adenoma hipofisario . |
| spellingShingle |
EZH2 proliferation 1schafer heidi, 2maggi ana luz Pituitary adenoma EZH2 proliferación adenoma hipofisario . Zlocowski , N Sosa, L Torres, AL EZH2 as a regulator of cell proliferation in pituitary tumors |
| topic_facet |
EZH2 proliferation 1schafer heidi, 2maggi ana luz Pituitary adenoma EZH2 proliferación adenoma hipofisario . |
| author |
Zlocowski , N Sosa, L Torres, AL |
| author_facet |
Zlocowski , N Sosa, L Torres, AL |
| author_sort |
Zlocowski , N |
| title |
EZH2 as a regulator of cell proliferation in pituitary tumors |
| title_short |
EZH2 as a regulator of cell proliferation in pituitary tumors |
| title_full |
EZH2 as a regulator of cell proliferation in pituitary tumors |
| title_fullStr |
EZH2 as a regulator of cell proliferation in pituitary tumors |
| title_full_unstemmed |
EZH2 as a regulator of cell proliferation in pituitary tumors |
| title_sort |
ezh2 as a regulator of cell proliferation in pituitary tumors |
| description |
Abstract:
Pituitary adenomas are the most frequent intracranial neoplasms mainly benign in nature. However, they can occasionally lead to malignant endocrinopathies. Epigenetic modifications are described among the various factors proposed as guidelines for pituitary tumorigenesis.
EZH2, the enzyme responsible for introducing the epigenetic mark H3K27m3, is overexpressed in various tumor phenotypes and significantly associated with increased proliferation and poor prognosis. In order to analyze the regulatory mechanisms involved in the change of the epigenetic profile and its impact on the proliferative behavior of pituitary adenomas, the variations of EZH2 and H3K27me3, cell cycle regulators, metabolic and proliferative activity of tumor pituitary cells were analyzed.
The experimental model of estrogen-induced prolactinoma in adult male Fisher rats and the GH3 somatolactotropic pituitary tumor line were used. Through western blot, the protein levels of EZH2 and H3K27me3 were analyzed in control and adenomatous glands. On these samples, the mRNA levels of the following cell cycle regulators were also determined: cdkn1a, cdk4, ccdn1 and tp53. The GH3 cell line was treated with GSK343, a specific EZH2 inhibitor, in order to analyze the impact that EZH2 has on cell metabolism and proliferation through the MTT and BrDU incorporation assays, respectively. H3K27me3 levels were examined by Western Blot.
It was determined that the levels of EZH2 and H3K27me3 were increased in the adenomatous glands, while the levels of cdkn1a decreased compared to what was observed in control pituitary glands. The tests carried out with GSK343 demonstrated a reduction in H3K27me3 along with a decrease in cell metabolism and proliferation. The methodologies were performed in triplicate and analyzed by t test (Western Blot and qPCR) or ANOVA-Post test Tukey (MTT and BrDU) with significance of p <0.05.
The results obtained suggest EZH2 as a regulator of cell proliferation in pituitary tumors, where the presence of the repressive mark H3K27me3 on the cdkn1a promoter could be responsible for mediating this regulation, postulating EZH2 as a possible therapeutic target.
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| publisher |
Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología |
| publishDate |
2021 |
| url |
https://revistas.unc.edu.ar/index.php/med/article/view/34913 |
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2024-09-03T21:02:45Z |
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I10-R327-article-349132024-04-15T16:19:09Z EZH2 as a regulator of cell proliferation in pituitary tumors EZH2 como regulador de la proliferación celular de los tumores hipofisarios A Zlocowski , N Sosa, L Torres, AL EZH2 proliferation 1schafer heidi, 2maggi ana luz Pituitary adenoma EZH2 proliferación adenoma hipofisario . Abstract: Pituitary adenomas are the most frequent intracranial neoplasms mainly benign in nature. However, they can occasionally lead to malignant endocrinopathies. Epigenetic modifications are described among the various factors proposed as guidelines for pituitary tumorigenesis. EZH2, the enzyme responsible for introducing the epigenetic mark H3K27m3, is overexpressed in various tumor phenotypes and significantly associated with increased proliferation and poor prognosis. In order to analyze the regulatory mechanisms involved in the change of the epigenetic profile and its impact on the proliferative behavior of pituitary adenomas, the variations of EZH2 and H3K27me3, cell cycle regulators, metabolic and proliferative activity of tumor pituitary cells were analyzed. The experimental model of estrogen-induced prolactinoma in adult male Fisher rats and the GH3 somatolactotropic pituitary tumor line were used. Through western blot, the protein levels of EZH2 and H3K27me3 were analyzed in control and adenomatous glands. On these samples, the mRNA levels of the following cell cycle regulators were also determined: cdkn1a, cdk4, ccdn1 and tp53. The GH3 cell line was treated with GSK343, a specific EZH2 inhibitor, in order to analyze the impact that EZH2 has on cell metabolism and proliferation through the MTT and BrDU incorporation assays, respectively. H3K27me3 levels were examined by Western Blot. It was determined that the levels of EZH2 and H3K27me3 were increased in the adenomatous glands, while the levels of cdkn1a decreased compared to what was observed in control pituitary glands. The tests carried out with GSK343 demonstrated a reduction in H3K27me3 along with a decrease in cell metabolism and proliferation. The methodologies were performed in triplicate and analyzed by t test (Western Blot and qPCR) or ANOVA-Post test Tukey (MTT and BrDU) with significance of p <0.05. The results obtained suggest EZH2 as a regulator of cell proliferation in pituitary tumors, where the presence of the repressive mark H3K27me3 on the cdkn1a promoter could be responsible for mediating this regulation, postulating EZH2 as a possible therapeutic target. Resumen: Los adenomas hipofisiarios son las neoplasias intracraneales más frecuentes principalmente de naturaleza benigna, aunque en ocasiones pueden derivar en endocrinopatías malignas. Entre los diversos factores propuestos como directrices de la tumorigénesis hipofisaria se describen las modificaciones epigenéticas. EZH2, enzima responsable de introducir la marca epigenética H3K27m3, está sobreexpresada en diversos fenotipos tumorales y significativamente asociada con un aumento en la proliferación y mal pronóstico. Con el objetivo de analizar los mecanismos regulatorios involucrados en el cambio del perfil epigenético y su impacto en el comportamiento proliferativo de los adenomas hipofisiarios, se analizaron las variaciones de EZH2 y H3K27me3, reguladores del ciclo celular, actividad metabólica y proliferativa de células hipofisarias tumorales. Se utilizó el modelo experimental de prolactinoma inducido por estrógeno (30mg) en ratas Fisher macho adultas y la línea tumoral hipofisaria somatolactotropa GH3. Mediante western blot se analizaron los niveles proteicos de EZH2 y H3K27me3 en glándulas controles y adenomatosas. Sobre estas muestras también se determinaron los niveles de ARNm de los siguientes reguladores del ciclo celular: cdkn1a, cdk4, ccdn1 y tp53. La línea celular GH3 fue tratada con GSK343, inhibidor específico de EZH2, con la finalidad de analizar el impacto que tiene EZH2 sobre el metabolismo y la proliferación celular mediante los ensayos de MTT e incorporación de BrDU respectivamente. Los niveles de H3K27me3 fueron examinados mediante Western Blot. Se determinó que en las glándulas adenomatosas los niveles de EZH2 y de H3K27me3 se encontraron incrementados, mientras que los niveles de cdkn1a disminuyeron respecto a lo observado en hipófisis controles. Los ensayos realizados con GSK343 demostraron una reducción de H3K27me3 acompañada de una disminución en el metabolismo y proliferación celular. Las metodologías fueron realizadas por triplicado y analizadas mediante t test (Western Blot y qPCR) o ANOVA-Post test Tukey (MTT y BrDU) con significancias de p<0.05. Los resultados obtenidos sugieren a EZH2 como regulador de la proliferación celular de los tumores hipofisarios, donde la presencia de la marca represiva H3K27me3 sobre el promotor de cdkn1a podría ser la responsable de mediar esta regulación, postulando a EZH2 como posible blanco terapéutico. . Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2021-10-12 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion texto texto texto https://revistas.unc.edu.ar/index.php/med/article/view/34913 Revista de la Facultad de Ciencias Médicas de Córdoba.; Vol. 78 No. Suplemento (2021): Suplemento JIC XXII Revista de la Facultad de Ciencias Médicas de Córdoba; Vol. 78 Núm. Suplemento (2021): Suplemento JIC XXII Revista da Faculdade de Ciências Médicas de Córdoba; v. 78 n. Suplemento (2021): Suplemento JIC XXII 1853-0605 0014-6722 http://creativecommons.org/licenses/by-nc/4.0 |