Our recent studies suggest a unique role of p53 during the early stage of cancer development. However, how p53 activation is regulated during TPA treatment remains elusive. We used murine skin epidermal JB6 promotion-sensitive (P+) and promotion resistant (P-) cells to observe differential expression of PTEN during TPA-induced p53 activation. Total PTEN expression was decreased in only P+ cells. Nuclear expression of PTEN increased and complex formation between PTEN and p53 occurred in P+ cells treated with TPA. Knocking down PTEN expression via siRNA inhibited TPA-induced Bax expression. Similar effects were seen with the p53 inhibitor, pifithrin-alpha. Cells that were transfected with siRNA to PTEN exhibited enhanced tumorigenicity. Our findings suggest PTEN mediates TPA-induced p53 activation.
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