CBX7 is a tumor suppressor in mice and humans.
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.
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.
Floriana
F
Forzati
Antonella
A
Federico
Pierlorenzo
P
Pallante
Adele
A
Abbate
Francesco
F
Esposito
Umberto
U
Malapelle
Romina
R
Sepe
Giuseppe
G
Palma
Giancarlo
G
Troncone
Marzia
M
Scarfò
Claudio
C
Arra
Monica
M
Fedele
Alfredo
A
Fusco
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D045744:Cell Line, Tumor; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor; D057809:HEK293 Cells; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D063150:Polycomb Repressive Complex 1; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
C503627:CBX7 protein, human; C519505:Cbx7 protein, mouse; D019927:Cyclin E; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D063150:Polycomb Repressive Complex 1; D056464:Histone Deacetylase 2