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PMID: 22214847 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

CBX7 is a tumor suppressor in mice and humans.

The Journal of clinical investigation ·Vol. 122 ·No. 2 ·2012-02-00 ·Pages 612-23

Forzati F, Federico A, Pallante P, Abbate A, Esposito F, Malapelle U, Sepe R, Palma G, Troncone G, Scarfò M, Arra C, Fedele M, Fusco A

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.

MeSH Terms
Adenocarcinoma/genetics,metabolism,pathology Adenocarcinoma of Lung Animals Cell Line, Tumor Cyclin E/genetics,metabolism Fibroblasts/cytology,physiology Gene Expression Regulation, Neoplastic/genetics Genes, Tumor Suppressor HEK293 Cells Histone Deacetylase 2/genetics,metabolism Humans Lung Neoplasms/genetics,metabolism,pathology Mice Mice, Knockout Polycomb Repressive Complex 1 Promoter Regions, Genetic Repressor Proteins/genetics,metabolism Tumor Suppressor Proteins/genetics,metabolism
Chemicals
CBX7 protein, human Cbx7 protein, mouse Cyclin E Repressor Proteins Tumor Suppressor Proteins Polycomb Repressive Complex 1 Histone Deacetylase 2
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Forzati Floriana
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia, Università di Napoli Federico II, Naples, Italy.
Federico Antonella
Pallante Pierlorenzo
Abbate Adele
Esposito Francesco
Malapelle Umberto
Sepe Romina
Palma Giuseppe
Troncone Giancarlo
Scarfò Marzia
Arra Claudio
Fedele Monica
Fusco Alfredo
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
1558-8238
DOI
10.1172/JCI58620
Published
2012-02-00
Epub
2012-00-03
Pages
612-23
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC3266782
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1172/JCI58620 PMC Full Text View journal details
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