Downregulation of p21/WAF1 expression by thymidylate synthase

We developed a cell system where expression of thymidylate synthase (TS), a n enzyme essential for DNA synthesis, can be modulated by a Zn2+-inducible promoter in MCF-7 cells, We found that overexpression of TS resulted in dow nregulation of p21 protein and mRNA levels. Statistical analysis demonstrat ed a significant downregulation of p21, but not a statistically significant decrease in p53 protein levels following TS induction. Since p21 is known to be transcriptionally activated by p53, these results suggest that TS dow nregulation of p21 may be occurring through a p53 independent mechanism in this in vitro cell system. In addition, cell cycle analysis demonstrated th at down regulation of p21 by TS resulted in a decreased G(1)/S ratio in MCF -7 cells.