Sapochnik, M.; Haedo, M.R.; Fuertes, M.; Ajler, P.; Carrizo, G.; Cervio, A.; Sevlever, G.; Stalla, G.K.; Arzt, E."Autocrine IL-6 mediates pituitary tumor senescence" (2017) Oncotarget. 8(3):4690-4702
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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.


Documento: Artículo
Título:Autocrine IL-6 mediates pituitary tumor senescence
Autor:Sapochnik, M.; Haedo, M.R.; Fuertes, M.; Ajler, P.; Carrizo, G.; Cervio, A.; Sevlever, G.; Stalla, G.K.; Arzt, E.
Filiación:Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA), CONICET-Partner Institute of the Max Planck Society, Buenos Aires, C1425FQD, Argentina
Servicio de Neurocirugía, Hospital Italiano, Buenos Aires, C1199ABD, Argentina
Departamento de Neurocirugía, Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Buenos Aires, C1428AQK, Argentina
Department of Clinical Research, Max Planck Institute of Psychiatry, Munich, Germany
Departamento de Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, C1428EGA, Argentina
Palabras clave:Autocrine; Benign tumor; IL-6; Pituitary tumor; Senescence; beta galactosidase; cyclin dependent kinase inhibitor 2A; growth hormone; interleukin 6; senescence associated beta galactosidase; short hairpin RNA; tumor marker; unclassified drug; animal experiment; animal model; animal tissue; Article; autocrine effect; carcinogenicity; cell aging; cell culture; cell invasion; cell proliferation; controlled study; enzyme activity; enzyme analysis; gene expression; gene silencing; human; human cell; human tissue; hypophysis adenoma; hypophysis tumor; in vitro study; in vivo study; interferon production; male; molecular cloning; mouse; nonhuman; pathogenesis; phenotype; protein expression; senescence; wild type
Página de inicio:4690
Página de fin:4702
Título revista:Oncotarget
Título revista abreviado:Oncotarget
CAS:beta galactosidase; growth hormone, 36992-73-1, 37267-05-3, 66419-50-9, 9002-72-6


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---------- APA ----------
Sapochnik, M., Haedo, M.R., Fuertes, M., Ajler, P., Carrizo, G., Cervio, A., Sevlever, G.,..., Arzt, E. (2017) . Autocrine IL-6 mediates pituitary tumor senescence. Oncotarget, 8(3), 4690-4702.
---------- CHICAGO ----------
Sapochnik, M., Haedo, M.R., Fuertes, M., Ajler, P., Carrizo, G., Cervio, A., et al. "Autocrine IL-6 mediates pituitary tumor senescence" . Oncotarget 8, no. 3 (2017) : 4690-4702.
---------- MLA ----------
Sapochnik, M., Haedo, M.R., Fuertes, M., Ajler, P., Carrizo, G., Cervio, A., et al. "Autocrine IL-6 mediates pituitary tumor senescence" . Oncotarget, vol. 8, no. 3, 2017, pp. 4690-4702.
---------- VANCOUVER ----------
Sapochnik, M., Haedo, M.R., Fuertes, M., Ajler, P., Carrizo, G., Cervio, A., et al. Autocrine IL-6 mediates pituitary tumor senescence. Oncotarget. 2017;8(3):4690-4702.