FGF2/FGFR1 pathway inhibition modulates the proliferation of secreting pituitary tumor cells
Pituitary neuroendocrine tumors (PitNET) progress and behavior is associated with the participation of numerous molecules, which could be proposed as therapeutic targets. A frequent alteration is the Fibroblast Growth Factor (FGF2) and its receptor type 1 (FGFR1), whose deregulation was observed in...
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| Formato: | Artículo revista |
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Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
2022
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| Acceso en línea: | https://revistas.unc.edu.ar/index.php/med/article/view/39085 |
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I10-R327-article-39085 |
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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 |
| format |
Artículo revista |
| topic |
Pituitary tumors FGFR1 Proliferation AZD4547 Tumores Hipofisarios FGFR1 Proliferación AZD4547 . |
| spellingShingle |
Pituitary tumors FGFR1 Proliferation AZD4547 Tumores Hipofisarios FGFR1 Proliferación AZD4547 . Turina, A Petiti, JP Sosa, LDV FGF2/FGFR1 pathway inhibition modulates the proliferation of secreting pituitary tumor cells |
| topic_facet |
Pituitary tumors FGFR1 Proliferation AZD4547 Tumores Hipofisarios FGFR1 Proliferación AZD4547 . |
| author |
Turina, A Petiti, JP Sosa, LDV |
| author_facet |
Turina, A Petiti, JP Sosa, LDV |
| author_sort |
Turina, A |
| title |
FGF2/FGFR1 pathway inhibition modulates the proliferation of secreting pituitary tumor cells |
| title_short |
FGF2/FGFR1 pathway inhibition modulates the proliferation of secreting pituitary tumor cells |
| title_full |
FGF2/FGFR1 pathway inhibition modulates the proliferation of secreting pituitary tumor cells |
| title_fullStr |
FGF2/FGFR1 pathway inhibition modulates the proliferation of secreting pituitary tumor cells |
| title_full_unstemmed |
FGF2/FGFR1 pathway inhibition modulates the proliferation of secreting pituitary tumor cells |
| title_sort |
fgf2/fgfr1 pathway inhibition modulates the proliferation of secreting pituitary tumor cells |
| description |
Pituitary neuroendocrine tumors (PitNET) progress and behavior is associated with the participation of numerous molecules, which could be proposed as therapeutic targets. A frequent alteration is the Fibroblast Growth Factor (FGF2) and its receptor type 1 (FGFR1), whose deregulation was observed in different neoplasms and could be involved in the regulation of cell proliferation. The objective was to determine the effect of FGFR1 inhibition on the proliferation of somatolactotroph tumor cells.
Somatolactotroph tumor cell line (GH3) cultures were stimulated with FGF2 (10 ng/mL) alone or co-incubated with FGFR1 inhibitor: AZD4547 (AZD; 0.1-1-5-10 µM) for 24 h, by triplicate in independent experiments. Cell viability was determined by MTT assay, proliferative response by BrdU incorporation, cell cycle phases from flow cytometry by Propidium Iodide staining, and apoptosis by DAPI staining. The expression of FGFR1, ERK1/2 and STAT3 total and phosphorylated was evaluated after incubation with FGF2 alone or co-incubated with AZD (5-10 µM) for 30 min by western blot. Statistics: ANOVA-Post test: Tukey.
GH3 cells showed a high expression of FGFR1. FGF2 incubation induced an increase of cell viability and BrdU incorporation, effect that was reversed by dose-dependent of AZD (p<0.05). The stimulation of proliferation induced by FGF2 was associated with an increase of phosphorylated ERK1/2 and STAT3 expression and S and G2/M phases, compared to control cells. In addition, co-incubation with AZD induced inhibition of ERK1/2 and STAT3 phosphorylation, with increased G1 phase and decreased S and G2/M phases vs. FGF2. Furthermore, a significant increase in apoptotic cells was observed when cells were co-incubated with AZD (5-10µM; p<0.05).
These findings show that FGF2/FGFR1/ERK1/2-STAT3 pathway is key in the modulation of proliferation in somalactotroph pituitary tumor cells, where by FGFR1 inhibitor use in secreting PitNETs, with high expression of the receptor, could be complement in the current therapies. |
| publisher |
Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología |
| publishDate |
2022 |
| url |
https://revistas.unc.edu.ar/index.php/med/article/view/39085 |
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AT turinaa fgf2fgfr1pathwayinhibitionmodulatestheproliferationofsecretingpituitarytumorcells AT petitijp fgf2fgfr1pathwayinhibitionmodulatestheproliferationofsecretingpituitarytumorcells AT sosaldv fgf2fgfr1pathwayinhibitionmodulatestheproliferationofsecretingpituitarytumorcells AT turinaa lainhibiciondelaviafgf2fgfr1modulalaproliferaciondecelulastumoraleshipofisariassecretantes AT petitijp lainhibiciondelaviafgf2fgfr1modulalaproliferaciondecelulastumoraleshipofisariassecretantes AT sosaldv lainhibiciondelaviafgf2fgfr1modulalaproliferaciondecelulastumoraleshipofisariassecretantes |
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2024-09-03T21:04:09Z |
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2024-09-03T21:04:09Z |
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I10-R327-article-390852024-04-15T16:14:45Z FGF2/FGFR1 pathway inhibition modulates the proliferation of secreting pituitary tumor cells La inhibición de la vía FGF2/FGFR1 modula la proliferación de células tumorales hipofisarias secretantes . Turina, A Petiti, JP Sosa, LDV Pituitary tumors FGFR1 Proliferation AZD4547 Tumores Hipofisarios FGFR1 Proliferación AZD4547 . Pituitary neuroendocrine tumors (PitNET) progress and behavior is associated with the participation of numerous molecules, which could be proposed as therapeutic targets. A frequent alteration is the Fibroblast Growth Factor (FGF2) and its receptor type 1 (FGFR1), whose deregulation was observed in different neoplasms and could be involved in the regulation of cell proliferation. The objective was to determine the effect of FGFR1 inhibition on the proliferation of somatolactotroph tumor cells. Somatolactotroph tumor cell line (GH3) cultures were stimulated with FGF2 (10 ng/mL) alone or co-incubated with FGFR1 inhibitor: AZD4547 (AZD; 0.1-1-5-10 µM) for 24 h, by triplicate in independent experiments. Cell viability was determined by MTT assay, proliferative response by BrdU incorporation, cell cycle phases from flow cytometry by Propidium Iodide staining, and apoptosis by DAPI staining. The expression of FGFR1, ERK1/2 and STAT3 total and phosphorylated was evaluated after incubation with FGF2 alone or co-incubated with AZD (5-10 µM) for 30 min by western blot. Statistics: ANOVA-Post test: Tukey. GH3 cells showed a high expression of FGFR1. FGF2 incubation induced an increase of cell viability and BrdU incorporation, effect that was reversed by dose-dependent of AZD (p<0.05). The stimulation of proliferation induced by FGF2 was associated with an increase of phosphorylated ERK1/2 and STAT3 expression and S and G2/M phases, compared to control cells. In addition, co-incubation with AZD induced inhibition of ERK1/2 and STAT3 phosphorylation, with increased G1 phase and decreased S and G2/M phases vs. FGF2. Furthermore, a significant increase in apoptotic cells was observed when cells were co-incubated with AZD (5-10µM; p<0.05). These findings show that FGF2/FGFR1/ERK1/2-STAT3 pathway is key in the modulation of proliferation in somalactotroph pituitary tumor cells, where by FGFR1 inhibitor use in secreting PitNETs, with high expression of the receptor, could be complement in the current therapies. El progreso y comportamiento de los tumores neuroendocrinos pituitarios hipofisarios (PitNET) está asociado a la participación de numerosas moléculas, que podrían ser utilizadas como blancos terapéuticos. Una alteración frecuente es la del Factor de Crecimiento Fibroblástico (FGF2) y su receptor tipo 1 (FGFR1), cuya desregulación fue observada en diferentes neoplasias y estaría involucrada en la regulación de la proliferación celular. El objetivo fue determinar el efecto de la inhibición del receptor FGFR1 sobre la proliferación de células tumorales somatolactotropas. Cultivos de la línea tumoral hipofisaria somatolactotropa (GH3) fueron estimulados con FGF2 (10ng/mL) solo o co-incubado con el inhibidor del receptor FGFR1: AZD4547 (AZD; 0,1-1- 5- 10 µM) por 24 h, por triplicado en experimentos independientes. Luego, se determinó la viabilidad celular por el ensayo de MTT, la respuesta proliferativa por la incorporación de BrdU, las fases del ciclo celular mediante citometría de flujo por tinción con Ioduro de Propidio y la apoptosis mediante tinción con DAPI. La expresión de FGFR1, ERK1/2 y STAT3 total y fosforilada fue evaluada luego de incubación con FGF2 solo o co-incubado con AZD (5-10 µM) por 30min mediante western blot. Estadística: ANOVA-Post test: Tukey. Las células GH3 presentaron una alta expresión de FGFR1. La incubación con FGF2 indujo el aumento de la viabilidad celular e incorporación de BrdU, efecto que fue revertido por AZD en manera dosis dependiente (p<0,05). El estímulo de la proliferación inducido por FGF2 fue asociado al aumento de la expresión de ERK1/2 y STAT3 fosforiladas y de las fases S y G2/M respecto a células control. La co-incubación con AZD indujo la inhibición de la fosforilación de ERK1/2 y STAT3, con aumento de la fase G1 y disminución de las fases S y G2/M vs. el estímulo con FGF2. Además, se observó un aumento significativo de células en apoptosis cuando en células co-incubadas con AZD (5-10µM; p<0,05). Estos hallazgos muestran que la vía FGF2/FGFR1/ERK1/2-STAT3 es clave en la modulación de la proliferación en las células tumorales hipofisaria somalactotropa, por lo cual el empleo del inhibidor de FGFR1 en PitNET secretantes, con alta expresión del receptor, podría complementar las terapias actuales. . Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2022-10-26 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion texto texto . https://revistas.unc.edu.ar/index.php/med/article/view/39085 Revista de la Facultad de Ciencias Médicas de Córdoba.; Vol. 79 No. Suplemento JIC XXIII (2022): Suplemento JIC XXIII Revista de la Facultad de Ciencias Médicas de Córdoba; Vol. 79 Núm. Suplemento JIC XXIII (2022): Suplemento JIC XXIII Revista da Faculdade de Ciências Médicas de Córdoba; v. 79 n. Suplemento JIC XXIII (2022): Suplemento JIC XXIII 1853-0605 0014-6722 http://creativecommons.org/licenses/by-nc/4.0 |