Artículos de revistas
Involvement of MEK/ERK1/2 and PI3K/Akt pathways in the refractory behavior of GH3B6 Pituitary tumor cells to the inhibitory effect of TGFß1
Fecha
2015-02Registro en:
Petiti, Juan Pablo; del Valle Sosa, Liliana; Sabatino, María Eugenia; Vaca, Alicia Maldré del Valle; Gutiérrez, Silvina; et al.; Involvement of MEK/ERK1/2 and PI3K/Akt pathways in the refractory behavior of GH3B6 Pituitary tumor cells to the inhibitory effect of TGFß1; Endocrine Society; Endocrinology; 156; 2; 2-2015; 534-547
0013-7227
1945-7170
Autor
Petiti, Juan Pablo
del Valle Sosa, Liliana
Sabatino, María Eugenia
Vaca, Alicia Maldré del Valle
Gutiérrez, Silvina
de Paul, Ana Lucia
Torres, Alicia Ines
Resumen
Pituitary tumor cells have a poor response to the growth inhibitory effect of TGFβ1, possibly resulting from the cross talk of TGFβ/Smads signal with other signaling pathways, an undescribed mechanism in these tumoral cells. To address this hypothesis, we investigated whether the mitogen-activated extracellular signal-regulated kinase (MEK)/ERK1/2 and phosphoinositide-3 kinase/protein kinase B (PI3K/Akt) pathways were able to regulate the antimitogenic effect of TGFβ1 on GH3B6 cells. TGFβ1 treatment decreased the cell proliferation and induced an activation of mothers against decapentaplegic homolog 2/3 (Smad2/3), effects that were potentiated by MEK and PI3K inhibitors, thus indicating the existence of a cross talk between TGFβ1/Smad with the MEK/ERK1/2 or PI3K/Akt pathways. In addition, through immunoprecipitation assays, a direct interaction was observed between Smad2/3-ERK1/2 and Smad2/3-Akt, which decreased when the GH3B6 cells were incubated with TGFβ1 in the presence of MEK or PI3K inhibitors, thereby suggesting that the ERK1/2- and Akt-activated states were involved. These Smad2/3-ERK1/2 and Smad2/3-Akt associations were also confirmed by confocal and transmission electron microscopy. These findings indicate that the TGFβ1-antimitogenic effect in GH3B6 cells was attenuated by the MEK/ERK1/2 and PI3K/Akt pathways via modulating Smad2/3 phosphorylation. This molecular mechanism could explain in part the refractory behavior of pituitary tumor cells to the inhibitory effect of TGFβ1.