AsianScientist (Jul. 5, 2011) – Scientists in Singapore have used a zebrafish model of hepatocellular carcinoma (HCC) to uncover new information about how this deadly form of liver cancer arises.
Although clinical studies of HCC patients together with studies using mice and other animal models have provided clues about how HCC develops, the disease is still poorly understood.
In a study published today in Disease Models & Mechanisms, Prof. Gong Zhiyuan and Dr. Serguei Parinov at the National University of Singapore used the zebrafish as a model system to study the role of the Ras oncogene in causing HCC.
Gong and Parinov generated zebrafish that were genetically engineered to express an oncogenic form of Ras in the liver. Fish that expressed the highest levels of oncogenic Ras all died rapidly of malignant liver cancer (mostly within 30 days), while fish with lower levels of oncogenic Ras survived for a longer period and did not develop full-blown liver cancer.
This suggests that only very high levels of Ras activity can cause HCC. Previous work had indicated that cancer cells from HCC patients always have abnormally high activation of the Ras cellular pathway. However, whether and how the Ras pathway actually causes liver cancer was not clear.
Although validation studies in patients with HCC are required, this work provides new evidence that drugs targeting the Ras pathway are a promising avenue for therapy. The researchers also believe that their zebrafish model may be a cost-effective platform for drug screening and identifying new therapeutic targets.
The article can be found at: Nguyen AT et al. (2011) A High Level Of Liver-Specific Expression Of Oncogenic KrasV12 Drives Robust Liver Tumorigenesis In Transgenic Zebrafish
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Source: The Company of Biologists.
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