Effects of overexpressing p14ARF on the apoptosis in human melanoma cells irradiated with γ-ray

Tumor suppressor ARF can induce cell cycle arrest or apoptosis by activating p53. In order to explore the molecular mechanism of the induction of apoptosis by p14(ARF), a human melanoma cell model overexpressing p14(ARF) was constructed. Present study indicated that in the cells overexpressing p14(ARF), p53 was accumulated in nucleus while it dispersed in cytosol in the control cells. Irradiated with gamma-ray, overexpressing p14(ARF) promoted the apoptosis of A375 cells, triggered Smac release from mitochondria to cytosol, and increased the expression of p53, Bax, Caspase-3, Caspase-9, p21(cip1) and p27(kip1). However, the protein level of Bcl-2 and phospho-ERK was down-regulated. These results suggested a possible mechanism of p14(ARF) in promotion of apoptosis.