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

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.

Lp16-PSP, A Member of YjgF/YER057c/UK114 Protein Family Induces Apoptosis and p21WAF1/CIP1 Mediated G1 Cell Cycle Arrest in Human Acute Promyelocytic Leukemia (APL) HL-60 Cells

“…findings suggest that Lp16-PSP resulted in the induction of p21 WAF1/CIP1 mediated G1 cell cycle arrest in HL-60 cells. Several studies have shown that induction of apoptosis and cell cycle arrest are the valuable strategies for cancer drug discovery[37][38][39]. However, at this stage, it's difficult to conclude the possible molecular mechanism of the action of Lp16-PSP and further support our experimental findings on the basis of previously reported information associated with the other members of YjgF/YER057c/UK114 family.Although antineoplastic, ribonuclease, inhibition of protein synthesis and antiviral activities of the other members of YjgF/YER057c/UK114 protein family has been reported[40][41][42][43][44][45], and afterward it was proven that translation inhibition was driven by endoribonucleolytic activity.…”

PDCD5 regulates cell proliferation, cell cycle progression and apoptosi

“…Opposite to what we observed for PDCD5, depletion of PDCD2 in human acute leukemia cells impairs their proliferation, induces cell cycle arrest and p53 activation while overexpression of PDCD2 facilitates cell growth in cancers (55,64). However, in gastric cancer cells, expression of PDCD2 seems to induce cell cycle arrest and apoptosis, which are also found to be p53-dependent (54). This suggests the connection between PDCD2 and cell cycle arrest might be tissue and cancer type-dependent.…”

“…PDCD1, often known as PD-1, is the member that has been most extensively studied and shown to negatively regulate T cell responses, in collaboration with its two ligands, PD-L1 and PD-L2 (51)(52)(53). In addition to PDCD5, other programmed cell death proteins are also known to play important roles in apoptosis and/or cell cycle progression (54)(55)(56)(57), and are also dysregulated in many types of human cancers (13,16,(58)(59)(60)(61)(62)(63). Opposite to what we observed for PDCD5, depletion of PDCD2 in human acute leukemia cells impairs their proliferation, induces cell cycle arrest and p53 activation while overexpression of PDCD2 facilitates cell growth in cancers (55,64).…”

PDCD2 sensitizes HepG2 cells to sorafenib by suppressing epithelial‑mesenchymal transition

“…Accumulating data demonstrated that PDCD2 is involved in the development of cancer. For example, the expression of PDCD2 is decreased in gastric cancer tissue, and it may induce gastric cancer cell growth arrest and apoptosis in a p53-dependent manner (4,5). PDCD2 serves as a tumor suppresser gene involved in the pathogenesis of osteosarcoma (3).…”