
<ArticleTitle><prot>p73</prot> cooperates with DNA damage agents to induce apoptosis in MCF7 cells in a <prot>p53</prot>-dependent manner.</ArticleTitle>
<AbstractText><prot>p73</prot>, a member of the <prot>p53</prot> family, can induce apoptosis in cancer cells. Since <prot>p53</prot>-mediated apoptosis can be augmented by various cancer chemotherapeutic agents, it has been hypothesized that the status of the endogenous <prot>p53</prot> gene in cancer cells is a key determinant in the outcome of cancer therapy. To determine whether <prot>p73</prot> can sensitize cancer cells to apoptosis by DNA damage agents, several MCF7 adenocarcinoma cell lines that inducibly express <prot>p73</prot> or <prot>p53</prot> under a tetracycline-regulated promoter were generated. We found that at relevant physiological levels, <prot>p73</prot>, but not <prot>p53</prot>, is capable of sensitizing MCF7 cells to apoptosis induced by chemotherapeutic agents. In addition, we found that <prot>p73</prot> can cooperate with the DNA damaging agent camptothecin to activate the initiator caspase 2. Furthermore, we found that <prot>p73</prot> can cooperate with DNA damaging agents or <prot>p53</prot> to induce some <prot>p53</prot> target genes and activate their promoters. In contrast, in MCF7E6 cells that ectopically express the human <prot>papillomavirus E6 oncogene</prot> and are functionally <prot>p53</prot>-null, the ability of <prot>p73</prot> to sensitize cells to apoptosis is abrogated. Taken together, these results suggest that a functional interaction between <prot>p53</prot> and <prot>p73</prot> in MCF7 cells leads to enhanced induction of apoptosis.</AbstractText>
