TL(I) AND TL(III) ALTER EGF-DEPENDENT EARLY SIGNALS REQUIRED FOR PC12 CELLS CYCLE ENTRY

PINO, M. T. L.; VERSTRAETEN, S.V

Buenos Aires

Congreso; XLVIX Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2013

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

We previously demonstrated that Tl alters PC12 cell cycle and cyclins expression. EGF (10 ng/ml) addition to cells failed to prevent Tl-mediated alterations in cell cycle. In the current study, the effects of Tl(I) and Tl(III) (100 uM) on the early (15-90 min) activation of EGFR/Ras/Raf/MEK/ERK and PI3K/Akt pathways were analyzedin the presence (EGF+ cells) or absence (EGF- cells) of added EGF. EGF+ cells had maximal p-EGRF levels after 15 min of EGF addition. Tl(I) and Tl(III) did not modify p-EGFR kinetics in EGF- and EGF+ cells. At this time, pERK-1 was decreased and pERK-2 increased in EGF+ cells respect to EGF- cells. Tl increased pERK-1 levels in EGF+ cells, effect that positively correlated with cyclin D1 levels after 24 h of cells exposure to Tl. Also, Tl decreased pERK-2 levels, which negatively correlated with cyclin D1 levels. In EGF- cells, pAKT increased progressively and was not affectedby Tl. On the contrary, in EGF+ cells, Tl significantly increased pAKT levels at 15 min of incubation, which positively correlated with cyclin D1 accumulation at 24 h of Tl exposure. Together, experimental evidence suggest that Tl(I) and Tl(III) cause a misbalance in EGF-dependent cell signaling that ultimately leads to the alteration of cell cycle progression in PC12 cells. Supported by grants of UBA (20020100100112) and CONICET (PIP112-200801-01977).