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Deadly liver cancer may be triggered by cells changing identity, UCSF study shows
Date:7/16/2012

A rare type of cancer thought to derive from cells in the bile ducts of the liver may actually develop when one type of liver cell morphs into a totally different type, a process scientists used to consider all but impossible. UCSF researchers triggered this kind of cellular transformationand caused tumors to form in miceby activating just two genes. Their discovery suggests that drugs that are able to target those genes may provide a way to treat the deadly cancer, known as cholangiocarcinoma. It also shows, yet again, how the process of scientific discovery involves serendipity as well as skill.

The study appears as an advanced online publication July 16, 2012 in the Journal of Clinical Investigation and will appear later in the August print edition.

The two cell types, hepatocytes and biliary cells, exist side by side in the liver, but don't normally change their "stripes" -- their cellular function -- let alone turn into each other. Scientists have therefore assumed that hepatocellular carcinomas, the most common kind of liver cancer, start in the hepatocytes and that cholangiocarcinomas, the bile duct cancers, start in the biliary cells.

Hepatocytes, which form the bulk of the liver, "are very good at making other hepatocytes," said Holger Willenbring, PhD, an associate professor of surgery, a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, and a senior author of the study. "They can divide many times but are restricted in the progeny they produce. They either produce more hepatocytes or, if something goes wrong, can cause hepatocellular carcinomas."

The study started when Xin Chen, PhD, an assistant professor of bioengineering and therapeutic sciences and a senior author of the manuscript, tried to make something go wrong in the hepatocytes as a way to explore the origins of hepatocellular carcinoma. Chen and her group hoped to induce the cancer in mice by acti
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Contact: Jennifer O'Brien
jennifer.obrien@ucsf.edu
415-502-6397
University of California - San Francisco
Source:Eurekalert

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