Regulation of pituitary tumors proliferation induced for the FGF2/FGFR1 pathway

Abstract: Dysregulation of the growth factors and their receptors could lead to abnormal growth and progression of pituitary tumors. Previously, we demonstrated an increase in the expression of Fibroblast Growth Factor 2 (FGF2) in the experimental prolactinomas development, suggesting its participat...

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Autores principales: Villafañe , FM, Petiti , JP, Torres , Al, Sosa , L
Formato: Artículo revista
Publicado: Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2021
Materias:
Pituitary tumors
FGF2
Proliferation
FGFR1
Tumores Hipofisarios
Proliferación
Acceso en línea:https://revistas.unc.edu.ar/index.php/med/article/view/35023
Aporte de:
Revista de la Facultad de Ciencias Médicas de Córdoba de Universidad Nacional de Córdoba
id I10-R327-article-35023
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
format Artículo revista
topic Pituitary tumors
FGF2
Proliferation
FGFR1
Tumores Hipofisarios
FGF2
Proliferación
FGFR1
spellingShingle Pituitary tumors
FGF2
Proliferation
FGFR1
Tumores Hipofisarios
FGF2
Proliferación
FGFR1
Villafañe , FM
Petiti , JP
Torres , Al
Sosa , L
Regulation of pituitary tumors proliferation induced for the FGF2/FGFR1 pathway
topic_facet Pituitary tumors
FGF2
Proliferation
FGFR1
Tumores Hipofisarios
FGF2
Proliferación
FGFR1
author Villafañe , FM
Petiti , JP
Torres , Al
Sosa , L
author_facet Villafañe , FM
Petiti , JP
Torres , Al
Sosa , L
author_sort Villafañe , FM
title Regulation of pituitary tumors proliferation induced for the FGF2/FGFR1 pathway
title_short Regulation of pituitary tumors proliferation induced for the FGF2/FGFR1 pathway
title_full Regulation of pituitary tumors proliferation induced for the FGF2/FGFR1 pathway
title_fullStr Regulation of pituitary tumors proliferation induced for the FGF2/FGFR1 pathway
title_full_unstemmed Regulation of pituitary tumors proliferation induced for the FGF2/FGFR1 pathway
title_sort regulation of pituitary tumors proliferation induced for the fgf2/fgfr1 pathway
description Abstract: Dysregulation of the growth factors and their receptors could lead to abnormal growth and progression of pituitary tumors. Previously, we demonstrated an increase in the expression of Fibroblast Growth Factor 2 (FGF2) in the experimental prolactinomas development, suggesting its participation in tumor development but the molecular mechanisms that generate this effect still now unknown. The aim was to determine the role of FGF2, receptor 1 (FGFR1) and the MEK-ERK1/2 pathway on the proliferation of pituitary tumor cells. Somatolactotroph (GH3) and corticotroph (ATt20) pituitary tumor cell lines stimulated with FGF2 (10 and 100 ng / mL) were used. The expression of FGFR1 was evaluated by western blot. Cell viability was determined by MTT assay after stimulation with FGF2 for 24-48h on medium with or without 10% serum. The proliferative response was analyzed by incorporation of BrdU for 24h and the MEK-ERK1/2 participation by ERK1/2 phosphorylation by western blot, after FGF2 stimulus for 30min. Additionally, the MEK inhibitor PD 98059 (50uM) was used. Statistics: ANOVA-Post test: Tukey. The expression of FGFR1 was higher in GH3 than in ATt20. FGF2 induced a significant increase in cell viability on GH3at 24 and 48h to both doses, while an increase (p> 0.05) was only observed in ATt20 after stimulation with FGF2 100ng/mL for 48h. Considering that FGF2 effect in GH3 was major, we continue working on this cell line. The expression levels of ERK1/2 phosphorylated increased after FGF2 (10 and 100ng / mL) stimulus for 30min (p˂0.05 vs Control). Cell viability and BrdU incorporation was significantly higher in the cultures treated with both doses to FGF2 in presence of serum, effect that was reversed by PD 98059. These findings show that FGF2/FGFR1/ERK1/2 pathway participates in the increase of proliferation in GH3 lactosomatotroph tumor cells, which present greater expression of FGFR1, effect that was enhanced in serum medium which would be represent part tumor microenvironment in the tissue.
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/35023
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spelling I10-R327-article-350232024-04-15T16:19:09Z Regulation of pituitary tumors proliferation induced for the FGF2/FGFR1 pathway Regulación de la proliferación de tumores hipofisarios inducidos por la vía FGF2/FGFR1 Villafañe , FM Petiti , JP Torres , Al Sosa , L Pituitary tumors FGF2 Proliferation FGFR1 Tumores Hipofisarios FGF2 Proliferación FGFR1 Abstract: Dysregulation of the growth factors and their receptors could lead to abnormal growth and progression of pituitary tumors. Previously, we demonstrated an increase in the expression of Fibroblast Growth Factor 2 (FGF2) in the experimental prolactinomas development, suggesting its participation in tumor development but the molecular mechanisms that generate this effect still now unknown. The aim was to determine the role of FGF2, receptor 1 (FGFR1) and the MEK-ERK1/2 pathway on the proliferation of pituitary tumor cells. Somatolactotroph (GH3) and corticotroph (ATt20) pituitary tumor cell lines stimulated with FGF2 (10 and 100 ng / mL) were used. The expression of FGFR1 was evaluated by western blot. Cell viability was determined by MTT assay after stimulation with FGF2 for 24-48h on medium with or without 10% serum. The proliferative response was analyzed by incorporation of BrdU for 24h and the MEK-ERK1/2 participation by ERK1/2 phosphorylation by western blot, after FGF2 stimulus for 30min. Additionally, the MEK inhibitor PD 98059 (50uM) was used. Statistics: ANOVA-Post test: Tukey. The expression of FGFR1 was higher in GH3 than in ATt20. FGF2 induced a significant increase in cell viability on GH3at 24 and 48h to both doses, while an increase (p> 0.05) was only observed in ATt20 after stimulation with FGF2 100ng/mL for 48h. Considering that FGF2 effect in GH3 was major, we continue working on this cell line. The expression levels of ERK1/2 phosphorylated increased after FGF2 (10 and 100ng / mL) stimulus for 30min (p˂0.05 vs Control). Cell viability and BrdU incorporation was significantly higher in the cultures treated with both doses to FGF2 in presence of serum, effect that was reversed by PD 98059. These findings show that FGF2/FGFR1/ERK1/2 pathway participates in the increase of proliferation in GH3 lactosomatotroph tumor cells, which present greater expression of FGFR1, effect that was enhanced in serum medium which would be represent part tumor microenvironment in the tissue. Resumen:  La desregulación de factores de crecimiento y sus receptores puede conducir al crecimiento anormal y a la progresión de tumores hipofisarios. Anteriormente, demostramos un aumento en la expresión del Factor de Crecimiento Fibroblástico 2 (FGF2) en el desarrollo de prolactinomas experimentales, sugiriendo su participación en el desarrollo tumoral, siendo desconocidos los mecanismos moleculares que generan este efecto. El objetivo fue determinar el rol de FGF2, el receptor 1 (FGFR1) y la vía MEK- ERK1/2 sobre la proliferación de células tumorales hipofisarias. Se utilizaron cultivos de líneas tumorales hipofisarias somatolactotropa (GH3) y corticotropa (ATt20) estimulados con FGF2 (10 y 100 ng/mL). La expresión del FGFR1 fue evaluada por western blot. La viabilidad celular fue determinada por el ensayo de MTT luego del estímulo con FGF2 por 24 y/o 48h, con 10% de suero o sin suero. La respuesta proliferativa fue analizada por incorporación de BrdU por 24h y la participación de MEK-ERK1/2 mediante la fosforilación de ERK1/2 por western blot luego de 30 min con FGF2. También se utilizó el inhibidor de MEK, PD 98059 (50uM). Estadística: ANOVA-Post test: Tukey. La expresión de FGFR1 fue mayor en GH3 que en ATt20. FGF2 indujo un aumento significativo de la viabilidad celular en GH3 con ambas dosis a 24 y 48h, mientras que en ATt20 solo se observó un aumento (p>0,05) luego del estímulo con FGF2 100ng/mL por 48h. Tomando en cuenta que la respuesta a FGF2 en GH3 fue mayor, continuamos trabajando en esta línea celular. Se observó un aumento notable de los niveles de expresión de ERK1/2 fosforilada inducida por FGF2 (10 y 100ng/mL) en 30min (p˂0.05 vs Control). La viabilidad celular e incorporación de BrdU fue significativamente mayor en los cultivos tratados con FGF2 con ambas dosis en presencia de suero, efecto que fue revertido por PD 98059. Estos hallazgos muestran que la vía FGF2/FGFR1/ERK1/2 participa en el aumento de la proliferación de las células hipofisarias tumorales lactosomatotropa GH3, que presentan mayor expresión del FGFR1, efecto que es potenciado en medio con suero, lo que representaría parte del microambiente en el que se encontrarían las células tumorales en un tejido.   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/35023 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

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