Targeted Disruption of PDCD2 Delays G1/S Transition in Lung Carcinoma by Inhibiting Cyclin D1 Transcription

Abstract

We previously reported on high expression of define PDCD2 in human malignancies. Knockdown of PDCD2 reduced the proliferation of leukemia and lung carcinoma cells. However, the mechanism by which PDCD2 reduces tumor proliferation remains unclear. This study tested the hypothesis that lowered PDCD2 would delay the proliferation of A549 lung carcinoma cells. Entry of A549 cells into S-phase was significantly (p-value 0.05) delayed when PDCD2 was knockdown. This correlated with a significant downregulation of cyclin D1, and AKT phosphorylation. Inhibition of the PI3K/AKT signaling pathway by Ly294002 decreased levels of PDCD2. These findings are consistent with a role for PDCD2 to mediate the entry of A549 cells into the cell cycle. Resting A549 cells showed PDCD2 localizing in the nucleus and plasma membrane and became diffuse with cell division, suggesting that PDCD2 is mitogen-dependent and may be involved in the proper timing of cell cycle. These findings may represent a promising venue to develop PDCD2 in clinical applications.