2025: Growth Signaling Pathways in the Pathogenesis and Treatment of Canine Cancer
Grant Status: Closed
Abstract
Hemangiosarcoma (HAS) is a common cancer in dogs that originates from cells lining the blood vessels. HAS can affect any dog, but is seen more often in German Shepherds, Skye Terriers, and Golden Retrievers. This suggests that this disease has a heritable component. Tumors arise when cells respond inappropriately to growth factors, allowing them to divide continuously in an uncontrolled fashion. Tumor suppressor genes contain or eliminate these rapidly dividing cells, but mutations in these genes can disable their ability to function correctly. Our laboratory is examining the idea that the loss of function of one of these tumor suppressor genes, PTEN, leads to the increased production of tumor growth factors. In our studies, we will examine the frequency of the mutations in the PTEN gene from dogs with HAS, and the relationship of these mutations to increased production of a specific tumor growth factor, VEGF. The results of our research could lead to tests for screening dogs for mutations in PTEN, and information could have an immediate and long-lasting impact on canine health when used judiciously for breeding decisions. We will also test the ability of a novel therapeutic approach to restore normal function within these cells as a treatment for HAS. Such work may lead the way for the further development of novel therapies for the treatment of canine hemangiosarcoma.
Publication(s)
Akhtar, N., Padilla, M. L., Dickerson, E. B., Steinberg, H., Breent, M., Auerbach, R., & Helfand, S. C. (2004). Interleukin-12 Inhibits Tumor Growth in a Novel Angiogenesis Canine Hemangiosarcoma Xenograft Model. Neoplasia, 6(2), 106–116. https://doi.org/10.1593/neo.03334
Dickerson, E. B., Thomas, R., Fosmire, S. P., Lamerato-Kozicki, A. R., Bianco, S. R., Wojcieszyn, J. W., … Modiano, J. F. (2005). Mutations of Phosphatase and Tensin Homolog Deleted from Chromosome 10 in Canine Hemangiosarcoma. Veterinary Pathology, 42(5), 618–632. https://doi.org/10.1354/vp.42-5-618
Lin, P.-Y., Fosmire, S. P., Park, S.-H., Park, J.-Y., Baksh, S., Modiano, J. F., & Weiss, R. H. (2007). Attenuation of PTEN increases p21 stability and cytosolic localization in kidney cancer cells: a potential mechanism of apoptosis resistance. Molecular Cancer, 14.
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