Sp1 upregulates expression of TRF2 and TRF2 inhibition reduces tumorigenesis in human colorectal carcinoma cells.

Telomeres are essential for the maintenance of genomic integrality, they enablecomplete DNA replication, organize subnuclear domains, and protect chromosome endsagainst fusion. Loss of telomere function in human cells results in the formation ofdicentric chromosomes and other abnormalities such as end-to-end fusions.TRF2 is aubiquitously expressed protein which binds directly to the tandem array of duplextelomeric repeats and is involved in the telomere structure and chromosome endprotection. Inhibition of TRF2 induces end-to-end chromosome fusions and growth arrestor apoptosis in human melanoma cells.Lack of TRF2 in ALT cells also caused PMLdependentp53 activation and loss of telomeric DNA.TRF2 over-expression is found inseveral human tumors such as breast carcinomas, liver hepatocarcinomas, lungcarcinomas and gastric carcinomas. This suggests that TRF2 may have a role intumorigenisis.Cancers of the gastrointestinal tract share numerous common geneticfeatures despite differing widely in incidence and out...