Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
CBX7 is a tumor suppressor in mice and humans
Floriana Forzati, … , Monica Fedele, Alfredo Fusco
Floriana Forzati, … , Monica Fedele, Alfredo Fusco
Published January 3, 2012
Citation Information: J Clin Invest. 2012;122(2):612-623. https://doi.org/10.1172/JCI58620.
View: Text | PDF | Corrigendum
Research Article Oncology

CBX7 is a tumor suppressor in mice and humans

  • Text
  • PDF
Abstract

The CBX7 gene encodes a polycomb group protein that is known to be downregulated in many types of human cancers, although the role of this protein in carcinogenesis remains unclear. To shed light on this issue, we generated mice null for Cbx7. Mouse embryonic fibroblasts derived from these mice had a higher growth rate and reduced susceptibility to senescence compared with their WT counterparts. This was associated with upregulated expression of multiple cell cycle components, including cyclin E, which is known to play a key role in lung carcinogenesis in humans. Adult Cbx7-KO mice developed liver and lung adenomas and carcinomas. In in vivo and in vitro experiments, we demonstrated that CBX7 bound to the CCNE1 promoter in a complex that included HDAC2 and negatively regulated CCNE1 expression. Finally, we found that the lack of CBX7 protein expression in human lung carcinomas correlated with CCNE1 overexpression. These data suggest that CBX7 is a tumor suppressor and that its loss plays a key role in the pathogenesis of cancer.

Authors

Floriana Forzati, Antonella Federico, Pierlorenzo Pallante, Adele Abbate, Francesco Esposito, Umberto Malapelle, Romina Sepe, Giuseppe Palma, Giancarlo Troncone, Marzia Scarfò, Claudio Arra, Monica Fedele, Alfredo Fusco

×

Figure 3

CBX7-dependent regulation of Ccne1 expression.

Options: View larger image (or click on image) Download as PowerPoint
CBX7-dependent regulation of Ccne1 expression.
   
(A) qRT-PCR on MEFs a...
(A) qRT-PCR on MEFs and tissues from WT and Cbx7-KO mice, including Cbx7–/– MEFs transiently transfected with the backbone vector (Cbx7–/–C) or whose Cbx7 expression had been restored (Cbx7–/–R), to detect Ccne1 expression. (B) EMSA performed with a radiolabeled CCNE1 promoter oligonucleotide incubated with 5 and 20 ng of the recombinant GST-CBX7 (lanes 2 and 3), GST-CBX7-CHROMO (lanes 5 and 6), or GST-CBX7-NOCHROMO (lanes 8 and 9) proteins. Where indicated, a 400-fold molar excess of unlabeled CCNE1 promoter oligonucleotide was added (lanes 4, 7, and 10). Further negative controls were obtained by incubating the recombinant proteins with a radiolabeled GAPDH promoter oligonucleotide (lanes 11 and 12). (C–E) Results of ChIP assays. CDKN2A and CDH1 promoters were used as positive controls, whereas GAPDH promoter and nonspecific IgG instead of anti-CBX7 were used as negative controls. (C) ChIP assay on HEK 293 cells transfected with CBX7-expressing or empty vector for binding of CBX7 to the CCNE1 promoter. (D) ChIP assay on MEFs for binding of endogenous Cbx7 to the Ccne1 promoter. (E) ChIP assay on MEFs for binding of endogenous Cbx7 and Hdac2 to the Ccne1 promoter. (F) CCNE1 promoter–driven luciferase activity, relative to activation of empty vector–transfected cells, in HEK 293 cells. Where indicated, 1 and 2 μg of CBX7 was cotransfected with the cyclin E–luc plasmid. *P < 0.05; **P < 0.01.
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts