Programmed cell death 2 protein induces gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis in a p53-dependent manner.

Abstract

Programmed cell death 2 (PDCD2) is a highly conserved nuclear protein, and aberrant PDCD2 expression alters cell apoptosis. The present study aimed to investigate PDCD2 expression in gastric cancer. Tissue specimens from 34 gastric cancer patients were collected for analysis of PDCD2 expression using immunohistochemistry, western blotting and qRT-PCR. Gastric cancer cell lines (a p53-mutated MKN28 line and a wild-type p53 MKN45 line) were used to assess the effects of PDCD2 overexpression. p53-/- nude mice were used to investigate the effect of PDCD2 on ultraviolet B (UVB)-induced skin carcinogenesis. The data showed that PDCD2 expression was reduced in gastric cancer tissue specimens, and loss of PDCD2 expression was associated with the poor survival of patients. PDCD2 expression induced gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis. The antitumor effects of PDCD2 expression were dependent on p53 expression in gastric cancer cells. Moreover, PDCD2 expression inhibited activity of the ATM/Chk1/2/p53 signaling pathway. In addition, PDCD2 expression suppressed UVB-induced skin carcinogenesis in p53+/+ nude mice, but not in p53-/- mice. The data from the present study demonstrated that loss of PDCD2 expression could contribute to gastric cancer development and progression and that PDCD2-induced gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis are p53-dependent.