Evidence of cellular senescence during the development of estrogen-induced pituitary tumors

SABATINO M. E.; PETITI J.P.; SOSA L.; PEREZ P.; GUTIÉRREZ S.; LEIMGRUBER C.; LATINI A. S.; TORRES A.I.; DE PAUL A.L.

ENDOCRINE - RELATED CANCER

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2015 vol. 22 p. 299 - 317

1351-0088

Although pituitary adenomas represent 25% of intracranial tumors, they are usually benign, with the mechanisms by which these tumors usually avoid an invasive profile and metastatic growth development still remaining unclear. In this context, cellular senescence might constitute a plausible explanation for the benign nature of pituitary adenomas. In the present study, we investigated the emergence of cellular senescence as a growth control mechanism during the progression of estrogen-induced pituitary tumors. The quantification of Ki67-immunopositive cells in pituitaries from estrogenized male rats after 10, 20, 40 and 60 days revealed that the mitogenic potential rate was not sustained for the whole period analyzed and successively decreased after 10 days of estrogen exposition. In addition, the expression of cellular senescence features, such as the progressive rise in the enzymatic SA-b-galactosidase activity, IL6, IL1b and TGFb expression was observed throughout pituitary tumor development. Furthermore, tumoral pituitary cells also displayed nuclear pATM expression, indicating activated DNA damage signaling, with a significant increase in p21 expression also being detected. The associations among DNA damage signaling activation, SA-b-galactosidase expression and p21 may provide a reliable Combination of senescence-associated markers for in vivo pituitary senescence detection. These results suggest a role for this cellular process in the regulation of pituitary cell growth. Thus, cellular senescence should be conceived as a contributing component to the benign nature of pituitary Adenomas, thereby influencing the capability of the pituitary gland to avoid unregulated cell proliferation.