Molecular Imbalance Characterizes Colon Cancer Cells

The interaction between the enzyme Src tyrosine kinase and a protein known as nuclear receptor hepatocyte nuclear factor 4alpha (HNF4alpha) has been implicated as an initiating factor in the development of colon cancer.

Normal human tissues express several variants of the HNF4A gene, classified as P1 and P2 variants. Some tissues, such as liver, have just one type of variant but the colon has both P1 and P2 variants. Investigators at the University of California, Riverside (USA) used advanced immunohistochemical techniques to determine the extent of HNF4alpha expression in colon cancer tumors and to correlate this expression with Src tyrosine kinase activity.

The Investigators reported in the January 30, 2012, online edition of the journal Proceedings of the [US] National Academy of Sciences that P1-HNF4alpha was either lost or localized in the cytoplasm (where it was chemically inactive) in approximately 80% of samples in a collection of 450 human colon cancer specimens taken from Stage III tumors. Staining for active Src tyrosine kinase revealed direct correlation between this enzyme activity and loss of HNF4alplha expression in this subset of samples.

“Loss of nuclear P1 HNF4alpha protein in the colon may be an early sign of colon cancer,” said senior author Dr. Frances Sladek, professor of cell biology and toxicology at the University of California, Riverside. “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. Some of these drugs are in clinical trials for colon cancer. It would be exciting to determine whether these drugs can maintain the P1 HNF4a protein levels, as well as inhibit the Src kinase activity.”

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University of California, Riverside