Picking the right seat in cancer

C-myc is an oncogene implicated in inducing genes involved in proliferation, while repressing genes involved in growth arrest. Companies like AVI BioPharma Inc. have been developing antisense inhibitors of the gene to treat cancers and other proliferative disorders. But a paper published in last week's Proceedings of the National Academy of Sciences describes a new way of targeting the oncogene based on the formation of a regulatory element within c-myc's promoter region.

Researchers from Cyternex Inc. (San Diego, Calif.) showed that transcription of c-myc is repressed by the formation of a chair-like DNA quadruplex structure from a 27-base pair sequence upstream from the gene. To demonstrate the importance of this DNA structure, they caused a 3-fold increase in c-myc transcriptional activity by introducing a mutation that disrupts the chair-like structure. They then showed that the small molecule TMPyP4, which is known to bind quadruplex DNA structures, stabilized the structure, repressing transcription of c-myc...