UC-Davis veterinarians uncover key protein for diagnosing, treating lymphoma

DAVIS, CALIF. — A protein recently identified by veterinary researchers at the University of California-Davis (UC-Davis) may be key to diagnosing and treating lymphoma in animals and humans.

Veterinarians, working with medical researchers at UC-Davis, found a protein that appears to play a key role in the formation of lymphoma and other tumors by inhibiting a tumor-suppressing gene.

"Results from this study suggest that a gene known as RNPC1 may play a key role in the development of lymphoma," explains Xinbin Chen, a veterinary oncologist at UC-Davis who led the study, which was published in the July 15 edition of Genes & Development.

In dogs, lymphoma occurs spontaneously and accounts for 6 percent of all canine cancers. Lymphoma occurs when a lymphocyte undergoes a malignant change and begins to multiply out of control, the university says. As the lymphocytes multiply rapidly, they eventually crowd out normal, healthy cells. In time, the cancerous lymphocytes accumulate in the lymph nodes, liver, spleen and other locations in the body.

For 30 years, researchers have known about a cancer-suppressing gene called p53. But p53 can also mutate and produce undesirable proteins. Earlier studies show mutations of the p53 protein in 60 percent of all cancerous human tumors. In recent years, scientists, including Chen and his colleagues at UC-Davis, have found that p53 mutations also are active in the formation or cancerous tumors in other mammals, including dogs, cats and horses, UC-Davis reports.

Those earlier studies, and the activity of the p53 gene led Chen's team to examine the RNPC1 gene, known to be an RNA-building protein.

In the new study, Chen's team was able to show that the RNPC1 gene inhibited the activity of the p53 gene and reduced levels of the p53 protein in these cells.

Data from the dog lymphoma tests showed that the RNPC1 gene is frequently overactive in dog lymphomas and may play a role in the formation of lymphomas by inactivating the p53 gene, UC-Davis says.

More studies are needed to analyze the expression of patterns of both RNPC1 and p53, Chen says, adding that because canine and human lymphoma processes are so similar, dogs may serve "both as a valuable sentinel for environmental causes of the disease and as a model for exploring its causes and treatments."

The study was funded in part by the National Institutes for Health and conducted through UC-Davis Cancer Center's Integrated Cancer Research Program, which is a collaboration of more than 200 investigators from more than a dozen scientific disciplines, including 19 veterinary oncologists and basic scientists at the UC-Davis School of Veterinary Medicine.

Chen's research team included Jin Zhang, project scientist; Seong-Jun Cho, postdoctoral fellow; Limin Shu, postdoctoral fellow; Wensheng Yan, project scientist; Teri Guerrero, clinical trials coordinator; associate professor Michael Kent; and assistant professor Katherine Skorupski; all of the Comparative Cancer Center, UC-Davis schools of medicine and veterinary medicine; and Professor Hongwu Chen of the UC-Davis Cancer Center.