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Updated: May 23, 2026
14:57
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Chronic restraint stress attenuates p53 function and promotes tumorigenesis
Zhaohui Feng1, Lianxin Liu, Cen Zhang
1Department of Radiation Oncology and Department of Pediatrics, Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903, USA.
Summary
Chronic stress promotes cancer growth in mice by reducing the effectiveness of the tumor suppressor protein p53. Elevated glucocorticoids mediate this effect via SGK1 and MDM2, highlighting stress as a factor in tumorigenesis.
Area of Science:
- Oncology
- Stress Physiology
- Molecular Biology
Background:
- Epidemiological studies suggest a link between chronic psychological stress and increased cancer risk.
- The direct in vivo mechanisms by which stress influences tumorigenesis remain largely unelucidated.
Purpose of the Study:
- To provide direct in vivo evidence that chronic stress promotes tumorigenesis.
- To elucidate the molecular mechanisms underlying stress-induced tumorigenesis, focusing on the p53 pathway.
Main Methods:
- Utilized a chronic restraint stress model in p53(+/-) mice exposed to ionizing radiation.
- Investigated the impact of chronic stress on p53 protein levels and function.
- Examined the role of glucocorticoids, SGK1, and MDM2 in mediating stress effects on p53.
- Assessed the growth of human xenograft tumors in stressed and non-stressed mice.
Main Results:
- Chronic restraint stress significantly promoted ionizing radiation-induced tumorigenesis in p53(+/-) mice.
- Chronic stress led to decreased levels and impaired function of the tumor suppressor p53.
- Stress-induced promotion of tumor growth was largely dependent on p53 status.
- Elevated glucocorticoids during stress mediated the reduction in p53 function via SGK1 induction and increased MDM2 activity.
Conclusions:
- Chronic stress directly promotes tumorigenesis in vivo.
- Attenuation of p53 tumor suppressor function is a key mechanism in stress-induced tumorigenesis.
- Glucocorticoids elevated during chronic stress play a crucial role in mediating these effects on p53.
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