Date Published: July 15, 2013
Publisher: Impact Journals LLC
Author(s): David Vindrieux, Baptiste Gras, Merce Garcia-Belinchon, Samia Mourah, Céleste Lebbe, Arnaud Augert, David Bernard.
Normal cells enter a senescent state upon aberrant oncogenic signals and this response inhibits tumor initiation and progression. It is now well admitted that intracellular and membrane localized oncogenes can illicit oncogene induced senescence. However, the effect of mitogenic growth factor on cellular senescence is so far largely unknown. Here we show that normal human dermal fibroblasts display a complex response to Platelet derived growth factor B (PDGFB) expression. Indeed, PDGFB expression induces, in the same cell population, both senescence and cellular transformation. Remarkably both populations are sustained with passages suggesting that transformed cells eventually enter a senescent state. This senescence state is p53 dependent as inhibiting the p53 pathway blocks the ability of PDGFB to induce senescence and results in strong cellular transformation increase upon PDGFB expression. The relevance of these observations is supported by the fact that human dermatofibrosarcoma protuberans, skin tumors arising from constitutive PDGFB production with little aggressiveness, also display some senescence hallmarks. Together these data support the view that PDGFB, a mitogenic growth factor, has a limited ability to induce senescence. We propose that this low level of senescence might decrease the transforming ability of this factor without totally abolishing it.
Tissue homeostasis is dependent upon cellular responses that cells will engage following various detrimental signals. Deregulation or loss of function of these responses leads to the accumulation of damages that might results in disease development. Oncogenic stresses are such detrimental signals that, if not properly recognized, cause cancer development . As a failsafe program in response to an oncogenic stress, cell will enter in a stable form of cell cycle arrest termed senescence. Senescent cells acquire some characteristics such as the secretion of numerous factors that reinforce the cell cycle arrest [2, 3] and allow the detection and elimination of the senescent “damaged” cells by the immune system [4, 5].