Human acute myeloid cell lines can be induced to differentiate into macrophage-like cells by phorbol esters. Differentiation is accompanied by cessation of cell proliferation and initiation of apoptosis. Many of these cell lines, like HL-60, are p53 deficient and therefore execute a differentiation-induced, p53-independent program of cell death. Evaluating changes in gene expression during a time course of PMA-induced HL-60 cell differentiation by DNA microarray analyses and RT-qPCR reveals up-regulation of several pro-apoptotic genes (ex. TNF, MCL1, EGR2, BCL3) and down-regulation of several anti-apoptotic genes (ex. BCL2, ANXA3, TSC22D3). Interestingly, RNA levels of p73 are unchanged, suggesting p73 does not substitute for the missing p53 function via activation of p73 gene transcription, however, we report here that p73 protein levels increase dramatically during the differentiation time course. By reintroducing p53 into HL-60 cells, we compare the changing gene expression profile during p53-mediated apoptosis versus that which occurs during phorbol ester-induced p73 accumulation through protein stabilization. Common and unique gene expression changes define the putative p73-dependent apoptosis program compared to p53-dependent apoptosis.
Citation Format: Michael Roberts, Rizwan Saffie, Harold Salmons, Mansoor Ghoto, Juliana Schneider, Jeffrey Forrester. Differentiation induced apoptosis in AML cells: The role of p73 in p53-independent versus p53-mediated apoptosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 346. doi:10.1158/1538-7445.AM2014-346