00978-A: Isolation of the Canine Telomerase Reverse Transcriptase (TERT) Subunit and Generation of Dominant-Negative Mutants for Telomerase Inhibition
Grant Status: Closed
AbstractCancer remains one of the leading causes of death in older dogs. Although surgical techniques, chemotherapy and radiation therapy have been refined over the past 30 years, for many types of cancer, survival rates remain low. Therefore, research has focused on identifying new ways to treat cancer, particularly focused on molecules and enzymes specifically produced by cancer cells. One of the most promising of these to emerge in recent years has been the enzyme telomerase. Telomerase activity bypasses the normal aging mechanism within cells, allowing them to divide indefinitely. Up to 90 percent of human and canine cancers have now been shown to possess telomerase activity, whilst normal cells do not. One component of telomerase, known as TERT, determines whether the enzyme becomes activated within cells. In humans, modification of TERT component has been used to create a molecule that inhibits telomerase activity. The TERT component can also be used in other ways, for instance to vaccinate patients against telomerase activity. However, although the gene that encodes TERT in dogs has been sequenced, its transcript has not yet been isolated, a vital pre-requisite for the development of future therapies. Therefore, the aim of this proposal is to isolate the canine TERT transcript. In addition, the ability of this transcript to provide telomerase activity will be tested in canine cells that do not normally possess telomerase activity.
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