Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 100, Issue 16, Pages 9354-9359Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1533295100
Keywords
carcinogenesis; cytokines; p21; transformation
Categories
Funding
- NIAID NIH HHS [R01-AI42310, R01 AI042310] Funding Source: Medline
- NIAMS NIH HHS [1R01AR45918, R01 AR045918, R01-ARO49610] Funding Source: Medline
- NINDS NIH HHS [R01 NS042809, NS-42809] Funding Source: Medline
Ask authors/readers for more resources
Macrophage migration inhibitory factor (MIF) is a mediator of host immunity and functions as a high, upstream activator of cells within the innate and the adaptive immunological systems. Recent studies have suggested a potentially broader role for MIF in growth regulation because of its ability to antagonize p53-mediated gene activation and apoptosis. To better understand MIF's activity in growth control, we generated and characterized a strain of MIF-knockout (MIF-KO) mice in the inbred, C57BL/6 background. Embryonic fibroblasts from MIF-KO mice exhibit p53-dependent growth alterations, increased p53 transcriptional activity, and resistance to ras-mediated transformation. Concurrent deletion of the p53 gene in vivo reversed the observed phenotype of cells deficient in MIR In vivo studies showed that fibrosarcomas induced by the carcinogen benzo[a]pyrene are smaller in size and have a lower mitotic index in IMIF-KO mice relative to their WT counterparts. The data provide direct genetic evidence for a functional link between MIF and the p53 tumor suppressor and indicate an important and previously unappreciated role for MIF in carcinogenesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available