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.
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Research Article Oncology

CBX7 is a tumor suppressor in mice and humans

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

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Figure 4

CBX7 interacts with HMGA1b.

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CBX7 interacts with HMGA1b. (A) HEK 293 cells were transfected with both...
(A) HEK 293 cells were transfected with both CBX7-V5 and HMGA1b expression plasmids. Cellular lysates were prepared, and equal amounts of proteins were subjected to IP with anti–CBX7-V5, anti-HMGA1, or nonspecific IgG, as indicated. The immunocomplexes were immunoblotted with reciprocal antibodies. As a positive control, 50 μg of transfected cell lysates were separated on the polyacrylamide gel as input. Et.Br., ethidium bromide. (B) Tissue lysates were prepared from WT embryos, and equal amounts of proteins were subjected to IP with anti-HMGA1 antibodies or nonspecific IgG. The immunocomplexes were immunoblotted with anti-CBX7 antibodies, for detection of the co-IP, or with anti-HMGA1 antibodies, for the IP control. As a positive control, 100 μg tissue lysates were used as input. Lanes were run on the same gel but were noncontiguous (white lines). (C) GST-HMGA1b or GST proteins immobilized on glutathione beads were used to bind CBX7-V5 from HEK 293 cells. The filter was probed with the anti–CBX7-V5 antibody.