Activation of the p53 pathway induces α-smooth muscle actin expression in both myeloid leukemic cells and normal macrophages
✍ Scribed by Paola Secchiero; Erika Rimondi; Maria Grazia di Iasio; Rebecca Voltan; Arianna Gonelli; Giorgio Zauli
- Publisher
- John Wiley and Sons
- Year
- 2012
- Tongue
- English
- Weight
- 918 KB
- Volume
- 227
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Abstract
A range of cell types of mesenchymal origin express α‐smooth muscle actin (α‐SMA), a protein that plays a key role in controlling cell motility and differentiation along the fibrocyte and myofibroblast lineages. Although α‐SMA is often expressed in stromal cells associated to a variety of cancers including hematological malignancies, up to now the role of anti‐cancer drugs on α‐SMA has not been deeply investigated. In this study, we demonstrated that Nutlin‐3, the small molecule inhibitor of the MDM2/p53 interactions, significantly up‐regulated the mRNA and protein levels of α‐SMA in normal macrophages as well as in p53^wild‐type^ but not in p53^mutated/null^ myeloid leukemic cells. The p53‐dependence of α‐SMA up‐regulation induced by Nutlin‐3 was demonstrated in experiments performed with siRNA for p53. Of note, Nutlin‐3 mediated up‐regulation of α‐SMA in OCI leukemic cells was accompanied by cell adhesion to plastic substrate and by reduced cell migratory response in transwell assays. Notably, the role of α‐SMA induction in the modulation of myeloid cell migration was clearly documented in α‐SMA gene knockdown experiments. In addition, Nutlin‐3 significantly up‐regulated α‐SMA expression in primary endothelial cells, but not in fibroblasts and mesenchymal stem cells (MSC). Conversely, transforming growth factor‐β1 up‐regulated α‐SMA in fibroblasts and MSC, but not in macrophages and endothelial cells. Taken together, these data indicate that Nutlin‐3 is a potent inducer of α‐SMA in both normal and leukemic myeloid cells as well as in endothelial cells. J. Cell. Physiol. 227: 1829–1837, 2012. © 2011 Wiley Periodicals, Inc.