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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 Article has an altmetric score of 4

CBX7 is a tumor suppressor in mice and humans

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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 1

Generation of Cbx7-KO mice.

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Generation of Cbx7-KO mice.
   
(A) Endogenous WT allele, targeting vect...
(A) Endogenous WT allele, targeting vector, and resulting KO allele. E, EcoRI; Neo, neomycin; Ex, exon. (B) Southern blot of representative Cbx7+/+ and Cbx7+/– ES cell clones. (C) Northern blot analysis of total RNA from kidneys, lungs and MEFs of Cbx7+/+, Cbx7+/–, and Cbx7–/– mice. The lengths of the WT Cbx7 transcript (2,900 bp) and the predicted truncated form after homologous recombination with the Cbx7-KO construct (380 bp) are shown. The absence of a 380-bp signal in both Cbx7+/– and Cbx7–/– mice is likely the result of instability of the short transcript. Actb expression analysis of the same blot is shown as control of RNA loaded. (D) Gross appearance of a representative 1-year-old Cbx7–/– mouse and a sex-matched Cbx7+/+ sibling. (E) Naso-anal length of cohorts of 20 mice, males or females, was measured at 12 months of age. Values are mean ± SD. *P < 0.05.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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