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 p16(Ink4a) and p14(Arf) 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 p14(Arf)/p53 and p16(Ink4a)/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 p16(Ink4a) and p14(Arf) expression in normal and tumor-derived prostate cells, affecting their growth depending on the status of the p16(Ink4a)/Rb and the p14(Arf)/p53 pathways.