CBX7 controls the growth of normal and tumor-derived prostate cells by repressing the Ink4a/Arf locus.
Control of cell proliferation by Polycomb group proteins (PcG) is an important facet of cellular homeostasis and its disruption can promote tumorigenesis. We recently described CBX7 as a novel PcG protein controlling the growth of normal cells. In an attempt to identify a putative role of CBX7 in tumorigenesis, we analysed CBX7 expression in a panel of cancer cell lines and primary tissues. CBX7 was highly expressed in three different prostate cancer cell lines and present at elevated levels in normal prostate. Ablation of CBX7 expression using short hairpin RNAs (shRNA) resulted in upregulation of p16Ink4a and p14Arf in both LNCaP and PC-3 prostate cell lines. CBX7 knockdown caused an impairment of cell growth that was dependent on the status of the p14Arf/p53 and p16Ink4a/Rb pathways in both normal and cancer prostate cells. CBX7 overexpression in LNCaP cells resulted in a slight growth advantage in both androgen-dependent and -independent conditions. Moreover, CBX7 expression cooperated with c-Myc in rendering LNCaP cells insensitive to growth arrest by androgen receptor inhibition. Together, these data suggest that CBX7 represses p16Ink4a and p14Arf expression in normal and tumor-derived prostate cells, affecting their growth depending on the status of the p16Ink4a/Rb and the p14Arf/p53 pathways.
Bernard
David
D
Laboratory of Molecular Virology, Faculty of Medicine, Free University of Brussels, Brussels, Belgium.
Martinez-Leal
Juan F
JF
Rizzo
Sian
S
Martinez
Dolores
D
Hudson
David
D
Visakorpi
Tapio
T
Peters
Gordon
G
Carnero
Amancio
A
Beach
David
D
Gil
Jesus
J
D000728:Androgens / Q000494:pharmacology; D049109:Cell Proliferation; D002478:Cells, Cultured; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D063150:Polycomb Repressive Complex 1; D011467:Prostate / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics / Q000378:metabolism*
D000728:Androgens; C503627:CBX7 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D025803:Tumor Suppressor Protein p14ARF; D063150:Polycomb Repressive Complex 1