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Updated: May 8, 2026

Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
Platelet-derived growth factor B induces senescence and transformation in normal human fibroblasts
David Vindrieux1, Baptiste Gras, Merce Garcia-Belinchon
1Inserm U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, F-69000, France.
Abstract:
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.
Insights
Platelet-derived growth factor B (PDGFB) can induce both senescence and cellular transformation in normal cells. This p53-dependent senescence response limits PDGFB
Area of Science:
- Cellular biology
- Oncology
- Molecular mechanisms of cancer
Background:
- Cellular senescence is a tumor suppressive mechanism triggered by oncogenic signals.
- The role of mitogenic growth factors, like Platelet-derived growth factor B (PDGFB), in inducing senescence is not well understood.
- Oncogene-induced senescence (OIS) is a known phenomenon, but the impact of growth factors on senescence requires further investigation.
Purpose of the Study:
- To investigate the effect of Platelet-derived growth factor B (PDGFB) on cellular senescence in normal human dermal fibroblasts.
- To determine the relationship between PDGFB-induced senescence and cellular transformation.
- To elucidate the role of the p53 pathway in PDGFB-mediated senescence.
Main Methods:
- Culturing normal human dermal fibroblasts.
- Inducing Platelet-derived growth factor B (PDGFB) expression.
- Assessing cellular senescence and transformation markers.
- Inhibiting the p53 signaling pathway.
Main Results:
- PDGFB expression induced a complex response, leading to both senescence and cellular transformation in the same cell population.
- Sustained passage of cells indicated that transformed cells eventually entered a senescent state.
- Inhibition of the p53 pathway abolished PDGFB-induced senescence and significantly increased cellular transformation.
- Human dermatofibrosarcoma protuberans, tumors with constitutive PDGFB, exhibited senescence hallmarks.
Conclusions:
- PDGFB exhibits a limited capacity to induce cellular senescence.
- The p53 pathway is crucial for mediating PDGFB-induced senescence.
- This partial senescence may attenuate but not eliminate the transforming potential of PDGFB.
- Findings are supported by observations in PDGFB-driven skin tumors, suggesting a role for senescence in modulating tumor aggressiveness.
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