Researchers at Stony Brook Medical Center has identified a family of genes related to liver cancer. They discovered in a mouse model that the loss of one specific gene (Iqgap2) in this family causes Hepatocellular carcinoma (HCC). If the other gene (Iqgap1) is present without the presence of Iqgap2 more severe damages could occur.
The research model will be published in the March issue of Molecular and Cellular Biology. Principal researcher Dr. Wadie F. Bahou, M.D., Professor of Medicine and Genetics, and colleagues commented that both genes will play a vital role in treating HCC by developing important targets for early diagnosis. This disease accounts for more than 80% of liver cancer in humans causing 500,000 to one million adult deaths annually worldwide.
Treatment for advanced HCC is often ineffective as a recently approved chemotherapy drug developed to treat metastatic liver cancer actually stabilized diseases instead of curing it. ‘This is an exciting development in the field of cancer research, as there is a tremendous need for targeted therapies for liver cancer,’ Dr. Bahou said.
‘ ‘The data resulting from our research provides important insights into genes that may predispose to HCC development,’ he added, further noting that the model is a valuable tool for testing therapeutic agents aimed at curing liver cancer.
Dr. Bahou stated that so far attempts to treat liver cancer has been difficult due to failure of developing effective animal disease models. According to a press release from the Stony Brook website, the animal disease model developed by the Stony Brook team is the closest to human disease model because of four main reasons:
- The disease closely resembles human HCC microscopically;
- does not require intervention from outside sources, such as chemically induced cancer models;
- is associated with a reproducible and very high incidence of HCC, and
- is strictly limited to HCC.
The detailed results of the research will be published in the March issue of Molecular and Cellular Biology in an article entitled ‘Development of Hepatocellular Carcinoma in Iqgap2-Deficient Mice Is Iqgap1-dependent.’
The removal of Iqgap2 gene using sophisticated techniques yield the development of HCC in the mice, confirming that Iqgap2 has a vital role in combating liver cancer. When the mice retained Iqgap1 without the presence of Iqgap2, the disease was further developed.
Additional experimentation showed that Iqgpap1 harnesses HCC, if Iqgap2 (the cousin gene) is not present, and inactivation of Iqgap1 in the mouse liver limits the aggressiveness due the deficiency of Iqgap2.
According to Dr. Bahou, the researchers are currently conducting similar genetic analyses in human liver cancer.
Co-researchers of the mouse study include lead author Valentina A. Schmidt, Ph.D., Department of Medicine; Carmine S. Chiariello, Ph.D., Program in Genetics; Encarnaci’oacute;n Capilla, Ph.D., Department of Pharmaological Sciences, and Frederick Miller, M.D., Department of Pathology. The research was supported by the National Institutes of Health.
