INHIBITION OF CDK2 KINASE-ACTIVITY BY METHYLSELENOCYSTEINE IN SYNCHRONIZED MOUSE MAMMARY EPITHELIAL TUMOR-CELLS

Methylselenocysteine (MSG), an organic selenium compound has significa nt anticarcinogenic activity against mammary tumorigenesis. Previous e xperiments have demonstrated that MSC and inorganic selenite inhibit m ammary cell (TM6 cell line) growth through different pathways, The pre sent investigation demonstrated that RISC arrested cells in S phase du ring the TM6 cell cycle, which was followed by cells entering apoptosi s at 48 h. Methylselenocysteine specifically affected the cdk2 kinase activity of the TM6 cells (54% reduction) at 16 h after release from g rowth arrest, The cdk4 kinase activity did not change during the cell cycle, confirming that cells had passed the G1 checkpoint and had ente red S phase, The amount of cyclin E associated with cdk2 was increased by MSC by the 12 h time point, thereby facilitating entry of cells in to S phase, Afterwards, cyclin E and cyclin A associated with cdk2 did not change for the remainder of the cell cycle. The data demonstrate that inhibition of mammary cell growth by MSC is mediated by alteratio ns in progression of cells through S phase, The decrease in cdk2 kinas e activity is coincident,with prolonged arrest in S phase. One consequ ence of prolonged arrest may be apoptosis.