UCR biologists make progress in colon cancer research

Courtesy of UCR Today

Recent studies by a team of UCR cell biologists have led to new prospects in the field of colon cancer, which annually kills 50,000 people in the United States. In a collaboration with Australian researchers, the team recognized a key association between the variants in the  “HNF4A” gene and the “Src kinase” protein, which may provide scientists with a better insight in the diagnosis and treatment for those afflicted with the ailment.

UC Riverside professor Frances Sladek and Graham Robertson from the University of Sydney, Australia, gathered 450 human colon cancer samples and studied their gene properties; 80 percent were found to have irregularities in the HNF4A gene variants, as reported by UCR Today.
Healthy human colons exhibit the gene HNF4A, which expresses two types of variants: the P1 and P2 protein; cancerous colons display diminishing activity in the P1 HNF4A protein.  “Since a Japanese group had published a paper a few years back showing that P1 but not P2 HNF4A expression was lost in some human colon cancers, we teamed up with the Australian group to look at a larger group of colon cancer samples,” stated Sladek in an email interview with the Highlander.
“Loss of nuclear P1 HNF4A protein in the colon may be an early sign of colon cancer,” explained Sladek in an article by UCR Today. “A healthy colon has a good but delicate balance of the two HNF4A variants. If you could prevent the loss of the P1 variant via drugs, you might be able to maintain a normal colon and prevent colon cancer.”
UC Riverside graduate and postdoctoral researcher Karthi Chellappa was the first author of the research paper who found that the  Src kinase protein modified the HNF4A protein—an association which had not been otherwise known in the scientific community.
The UC Riversde  group found that activated Src kinase modifies the P1 but not the P2 variant.  “Not only did we also see a loss of P1 HNF4A in the samples but we also saw the P1-HNF4A outside of the nucleus, just as we would  predict from our cell based studies with Src,” said Sladek. Results from the study have been documented in the “Proceedings of the National Academy of Sciences.” Drugs for the suppression of the activity of the Src protein are already available and are even in clinical trials. Other factors that may leave others more prone to colon cancer include DNA sequence variations in the HNF4A gene, with SNPs or “single nucleotide polymorphisms” being the most common one.
Colon cancer often starts out as benign polyps on the walls of the large intestine or rectum, where they have the possibility of turning cancerous. Colonoscopies can reduce the risk of colon cancer through the ability to detect and prevent adenoma polyps. Depending on the stage to which one is diagnosed those afflicted with colon cancer may undergo treatments such as surgery, chemotherapy and radiation therapy.
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