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Repeated Liver Cell Proliferation, a Cause for Liver Cancer

mor cells," said Karin. Blocking JNK prevents liver injury but also inhibits liver regeneration, so the timing and context of activation are very important, he added.

"In this research, we set out to identify what causes inflammation in response to liver injury, as well as what stimulates the proliferation of surviving hepatocytes," said Karin. "Since we previously knew that JNK activity is required for normal liver cell proliferation, we wondered if the same activity is required for production of liver cancer in carcinogen-exposed mice. The results were clear JNK1 is critical for tumor development."

The scientists genetically removed JNK1 to test if its increased activation, caused by the absence of IKK?ò, was responsible for accelerated tumor development. When JNK1 was removed, the number and size of cancerous liver tumors decreased, and the tumors grew more slowly. Increased JNK1 activation was found in diseased liver and tumors when compared to normal tissue.

Hepatocellular carcinoma (HCC), the most common form of liver cancer, is the third leading cause of cancer deaths worldwide. Its major risk factors are persistent infection with hepatitis B and C viruses, and exposure to toxic chemicals, including alcohol ?V all of which cause chronic liver injury and inflammation. Although not common in the United States., the incidence of HCC is on an upward trajectory, with little hope for treatment or cure through chemotherapy, radiation or other traditional cancer treatments.

"We now understand development of liver cancer in mice. Since inflammation drives both damage and regeneration in liver tissue, it is the repeating cycle of damage, inflammation and regeneration that leads to liver cancer," said Karin. "However, this knowledge is not satisfactory until we find out if it applies to humans."

Source: Eurekaert
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