Interleukine 6 contribution to cellular proliferation and senescence in pituitary tumours

SABATINO ME; GENOVESE DM; GRONDONA E; SOSA LDV; PÉREZ P; GUTIÉRREZ S; TORRES A; DE PAUL AL

Mar del Plata

Congreso; Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2015

Pituitary tumors are mostly benign, suggesting the participation of intrinsic mechanisms as cellular senescence, aprogram with anti-tumorigenic potential. In previous studies we showed evidence of cellular senescence inexperimental pituitary tumors development. Inflammatory secretome, in particular IL-6 cytokine, regulates cellularsenescence. In this study we evaluated IL-6 contribution in cellular proliferation and senescence of normal andtumoral pituitaries. Primary cultures from normal or 40 days-estrogenized Wistar male rats were treated with IL-6 orwith LPS alone or after BFA (secretion inhibitor) or BAY (NF-kB blocker) incubation. The proportion of SA-b-gal(senescence) or Ki67 (proliferation) positive cells was evaluated. Exogenous IL-6 decreased normal and tumoral cellproliferation while increased senescent cells number only under tumoral setting. Also, LPS, exclusively through itssecreted factors, raised the senescent cells proportion in normal and tumoral conditions and also induced tumoral cellproliferation. The NF-kB blockage by BAY alone or in combination with LPS increased cellular senescence andshowed a dual role toward proliferation control in tumoral cells. These data suggest that IL-6 might play a relevantrole in the pituitary tumor growth control, and NF-kB may act as a key regulator between pituitary cell proliferationand senescence in tumorigenesis.