The alternate protein from the INK4a/ARF locus on chromosome 9, p14ARF is a tumor suppressor gene that regulates the activity of the tumor suppressor p53. We have noted p53-independent effects of p14ARF on adenovirus replication during the construction of a replication defective adenovirus in HEK-293 cells lacking demonstrable p53 function. We have since developed a p14ARF inducible cell line that clearly demonstrates a p53-independent role for p14ARF in regulating viral replication. Based on this observation we are attempting to develop an adenovirus vector that will only replicate in cells that have lost the ability to appropriately suppress E2F transcriptional activity. Since inappropriate and unregulated cell proliferation is a hallmark of all cancer, it is possible to develop a virus that will only replicate in tumor cells with high levels of dysregulated E2F activity.

Adenoviral Targeting of Dysregulated E2F Activity with p14
Principal Investigator: James W. Rocco MD, PhD
Group Members: Michael Rho, MD; Thongchai Bhongmakapat, MD