Texas scientists discover how a hepatitis C protein promotes liver cancer

12/01/05

GALVESTON, Texas--Scientists at the University of Texas Medical Branch at Galveston (UTMB) have identified a key biochemical connection between the hepatitis C virus and liver cancer.

The molecular mechanism is similar to the one that links the human papilloma virus (HPV), the cause of genital warts, and cervical cancer, according to Dr. Stanley M. Lemon, the senior author of a paper on the discovery that will be published this week in the online early edition of the Proceedings of the National Academy of Sciences.

"What we've found is that one of the hepatitis C virus proteins targets a cell protein that is crucial for suppressing the development of tumors, interfering with its ability to control cell proliferation," Lemon said. "By knocking out this 'tumor suppressor' and promoting the proliferation of liver cells, this viral protein is setting up the liver for cancer."

According to the federal Centers for Disease Control and Prevention, about 85 percent of liver cancer cases in the United States occur in people infected by the hepatitis C virus. Approximately 200 million people worldwide suffer from chronic hepatitis C, which can persist in the body for decades after an initial infection, often causing so much liver damage that a transplant may be a patient's only chance for survival. The most effective treatment available, interferon therapy, works only about half the time and often causes debilitating side effects. Those who fail treatment are at risk for fatal cirrhosis or developing liver cancer.

Researchers have known for a long time that hepatitis C virus infection can lead to liver cancer. But how the virus goes about this has been unclear.

The UTMB group discovered that the tumor-suppressing retinoblastoma protein is present at markedly reduced levels in cells containing a hepatitis C virus "replicon," a large piece of hepatitis C genetic material that is able to reproduce itself in cultured cells and also able to produce proteins made by hepatitis C viruses. "The replicon experiments enabled us to identify a protein known as NS5B that attaches to the retinoblastoma protein, a critical tumor suppressor, and accelerates its breakdown," Lemon said. He continued: "The way NS5B docks with the retinoblastoma protein is biochemically almost identical to the way a protein made by human papilloma virus does so to produce similar cancer-promoting results. That's interesting, because the two viruses are so different --HPV is a DNA virus, while hepatitis C is composed of RNA."

Understanding just how hepatitis C infection leads to the development of cancer is of critical importance, Lemon said. With no one "silver bullet" cure for hepatitis C on the horizon, he explained, researchers must use new knowledge to maximize the effectiveness of various virus-fighting therapies now under development, managing the care of chronically infected patients in ways that will best help them avoid liver cancer.

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