The cancer-testis antigen BORIS phenocopies the tumor suppressor CTCF in normal and neoplastic cells

摘要: BORIS and CTCF are paralogous, multivalent 11-zinc finger transcription factors that play important roles in organizing higher-order chromatin architecture. is a cancer-testis antigen with poorly defined function cancer, although it has been hypothesized to exhibit oncogenic properties. CTCF, however, postulated as candidate tumor suppressor. We collated the genetic lesions from multiple cancers identified using high-throughput genomics. In BORIS, nonsense missense mutations evenly distributed. recurrent mostly clustered conserved zinc domain at residues critical for contacting DNA ion co-ordination. Three common both proteins. used an inducible lentivector express wildtype or primary cells cancer cell lines order define their functional differences. Both caused significant decrease proliferation clonogenic capacity, without alteration of specific cycle phases. conferred protective effects some during UV damage-induced apoptosis. Using bioluminescent MCF-7 orthotopic breast model vivo, we demonstrated suppressed growth. These findings provide further evidence behaves suppressor, show similar growth inhibitory effect vitro vivo. Hence, acquired may disrupt these functions, thereby contributing development.