Cyclin a but not cyclin D1 is essential for c‐myc‐modulated cell‐cycle progression

The proto‐oncogene c‐myc is a key player in cell‐cycle regulation and is deregulated in a broad range of human cancers and cell proliferation disorders. Here we reported that overexpression of c‐myc in human embryonic lung fibroblasts (HEL) that have low endogenous c‐myc enriched S phase cells with increased expression of cyclin D3, E, A, Cdk2, and Cdk4, and decreased expression of p21 and p27. To the opposite, using RNAi to downregulate c‐myc expression in A549 cells that have high endogenous c‐myc enriched G1 phase cells with decreased expression of cyclin D3, E, A, Cdk2, Cdk4, and increased expression of p21 and p27. We found that cyclin A expression was the most susceptive to changes in c‐myc levels and essential in c‐myc‐modulated cell cycle pathway via co‐transfection, however, cyclin D1 showed no change between treated and control groups in either HEL or A549 cells. Our results indicated that upregulation of c‐myc expression promotes cell cycling in HEL cells, whereas downregulation of c‐myc expression causes G1 phase arrest in A549 cells, and the c‐myc‐mediated cell‐cycle regulation pathway was dependent on cyclin A and involved cyclin D3, E, Cdk2, Cdk4, p21, and p27, but not cyclin D1. J. Cell. Physiol. 210: 63–71, 2007. © 2006 Wiley‐Liss, Inc.

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