Resumen de Cooperative role between p21cip1/waf1 and p27kip1 in premature senescence in glandular proliferative lesions in mice

Rosa Ana García Fernández, Pilar García Palencia, C. Suarez, M.A. Sánchez Pérez, Gabriel Gil Gómez, B. Sánchez Maldonado, Eduardo Ricardo Rollán Landeras, Juan Martín Caballero, Juana María Flores Landeira

• Cellular senescence has been considered a novel target for cancer therapy. It has also been pointed out that p21cip1/waf1 and p27kip1 cyclin-dependent kinase inhibitors (CKIs) play a role in cellular senescence in some tumor types. Therefore, in order to address the possibility of a cooperative role between p21 and p27 proteins in senescence in vivo we analyzed cellular senescence in spontaneous glandular proliferative lesions (adrenal, thyroid and pituitary glands) in a double-KO mice model, using ?H2AX, p53, p16, PTEN and Ki67 as senescence markers. The results obtained showed that p21p27 double-null mice had the lowest number of ?H2AX positive cells in glandular hyperplasias and benign tumors. Also, in this group, Ki67 proliferation index correlated with a lower immunohistochemical expression of ?H2AX and p53. The expression of p16 and PTEN do not seem to cause synergism of senescence in the benign lesions analyzed in p21p27 double-KO mice. These observations suggest an intrinsic cooperation between p21 and p27 CKIs in the activation of stress-induced cellular senescence and tumor progression in vivo, which would be a physiological mechanism to prevent tumor cell proliferation.