ArticleHepatology (Baltimore, Md.)2011
PUMA-mediated apoptosis drives chemical hepatocarcinogenesis in mice.
Article in Hepatology (Baltimore, Md.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 101 citations in OpenAlex.
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- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- Multifaceted roles of aerobic glycolysis and oxidative phosphorylation in hepatocellular carcinoma.PeerJ · 2023Review
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- Phosphorylation of NF-κBp65 drives inflammation-mediated hepatocellular carcinogenesis and is a novel therapeutic target.Journal of experimental & clinical cancer research : CR · 2021Article
- Persistent hepatocyte apoptosis promotes tumorigenesis from diethylnitrosamine-transformed hepatocytes through increased oxidative stress, independent of compensatory liver regeneration.Scientific reports · 2021Article
- PIDDosome-induced p53-dependent ploidy restriction facilitates hepatocarcinogenesis.EMBO reports · 2020Article
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- PTTG1 is involved in TNF-α-related hepatocellular carcinoma via the induction of c-myc.Cancer medicine · 2019Article
- The Carcinogenic Agent Diethylnitrosamine Induces Early Oxidative Stress, Inflammation and Proliferation in Rat Liver, Stomach and Colon: Protective Effect of Ginger Extract.Asian Pacific journal of cancer prevention : APJCP · 2019Article
- Review
- p53 Up-regulated Modulator of Apoptosis Induction Mediates Acetaminophen-Induced Necrosis and Liver Injury in Mice.Hepatology (Baltimore, Md.) · 2019Article
- Aberrant expression and high-frequency mutations ofExperimental and therapeutic medicine · 2019Article
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- Two Sides of the Same Coin - Compensatory Proliferation in Regeneration and Cancer.Advances in experimental medicine and biology · 2019Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledHepatocyte death and proliferation contribute to hepatocellular carcinoma development after carcinogen exposure or chronic liver inflammation. However, the role and the molecular targets of hepatocyte death in relation to compensatory proliferation have not been fully characterized. In this study, we investigated the role of p53 up-regulated modulator of apoptosis (PUMA), a BH3-only protein important for both p53-dependent and -independent apoptosis, in a diethylnitrosamine (DEN)-induced liver carcinogenesis model. PUMA deficiency significantly decreased the multiplicity and size of liver tumors. DEN treatment induced p53-independent PUMA expression, PUMA-dependent hepatocyte death, and compensatory proliferation. Furthermore, inhibition or deletion of c-jun N-terminal kinase 1 (JNK1) abrogated PUMA induction, hepatocyte death, and compensatory proliferation.
conclusionThese results provide direct evidence that JNK1/PUMA-dependent apoptosis promotes chemical hepatocarcinogenesis through compensatory proliferation, and suggest apoptotic inducers as potential therapeutic targets in liver injury and cancer.
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