info:eu-repo/semantics/article
Autocrine IL-6 mediates pituitary tumor senescence
Fecha
2017-01Registro en:
Sapochnik, Melanie Denise; Haedo, Mariana Raquel; Fuertes, Mariana; Ajler, Pablo; Carrizo, Guillermo; et al.; Autocrine IL-6 mediates pituitary tumor senescence; Impact Journals LLC; Oncotarget; 8; 3; 1-2017; 4690-4702
1949-2553
CONICET Digital
CONICET
Autor
Sapochnik, Melanie Denise
Haedo, Mariana Raquel
Fuertes, Mariana
Ajler, Pablo
Carrizo, Guillermo
Cervio, Andrés
Sevlever, Gustavo
Stalla, Günter K.
Arzt, Eduardo Simon
Resumen
Cellular senescence is a stable proliferative arrest state. Pituitary adenomas are frequent and mostly benign, but the mechanism for this remains unknown. IL-6 is involved in pituitary tumor progression and is produced by the tumoral cells. In a cell autonomous fashion, IL-6 participates in oncogene-induced senescence in transduced human melanocytes. Here we prove that autocrine IL-6 participates in pituitary tumor senescence. Endogenous IL-6 inhibition in somatotroph MtT/S shRNA stable clones results in decreased SA-β-gal activity and p16INK4a but increased pRb, proliferation and invasion. Nude mice injected with IL-6 silenced clones develop tumors contrary to MtT/S wild type that do not, demonstrating that clones that escape senescence are capable of becoming tumorigenic. When endogenous IL-6 is silenced, cell cultures derived from positive SA-β-gal human tumor samples decrease the expression of the senescence marker. Our results establish that IL-6 contributes to maintain senescence by its autocrine action, providing a natural model of IL-6 mediated benign adenoma senescence.