hide
Free keywords:
ONCOGENE-INDUCED SENESCENCE; PROOPIOMELANOCORTIN GENE-EXPRESSION;
GROUP-A PROTEINS; CELLULAR SENESCENCE; ANTERIOR-PITUITARY;
ADRENOCORTICOTROPIN SECRETION; FOLLICULOSTELLATE CELLS; STEM-CELLS;
ADENOMAS; GROWTHOncology; Cell Biology; senescence; IL-6; pituitary tumor; benign tumor; autocrine;
Abstract:
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-beta-gal activity and p16(INK4a) 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-beta-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.
