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Family Of Liver Cancer Genes

By Staff

{image- www.boldsky.com} Washington: A new study on mice, conducted by an interdisciplinary team of researchers at Stony Brook University Medical Center, has reported the discovery of a family of genes linked to the development of liver cancer.

The study was led by principal Investigator Wadie F. Bahou, M.D., Professor of Medicine and Genetics, and colleagues, who discovered in a mouse model that losing one specific gene (Iqgap2) in this family may lead to Hepatocellular carcinoma (HCC).

The investigators also found that a more aggressive form of the disease occurs when another member of the gene family (Iqgap1) is turned on.

According to Dr. Bahou the findings about the two genes show that both genes could be considered as the basis for the development of important targets for early diagnosis and/or treatment of HCC.

HCC is responsible for causing more than 80 percent of all liver cancer in humans, leading to death in 500,000 to 1 million adults annually worldwide.

While the treatment for advanced HCC is usually ineffective, a recently approved chemotherapy drug developed for the treatment of metastatic liver cancer provides disease stabilization but not a cure.

"This is an exciting development in the field of cancer research, as there is a tremendous need for targeted therapies for liver cancer. The data resulting from our research provides important insights into genes that may predispose to HCC development," he adds, further noting that the model is a valuable tool for testing therapeutic agents aimed at curing liver cancer," emphasized Dr. Bahou.

He described that efforts to treat liver cancer have been difficult without appropriate animal models of disease till date.

He said that the model generated by the Stony Brook team is the closest to human disease because the disease is similar to human HCC microscopically and does not require intervention from outside sources, such as chemically induced cancer models. it is also linked to a reproducible and very high incidence of HCC, and is strictly limited to HCC.

The researchers collectively found that Iqgap1 and Iqgap2 have functionally different roles in hepatocellular carcinogenesis. They found that after removing the Iqgap2 gene using sophisticated genetic techniques, the mice developed HCC.

This confirmed that Iqgap2 has a fundamentally important protective role against the development of liver cancer.

It was also seen that when mice retained Iqgap1, the cousin gene of Iqgap2, the animals developed more advanced disease. It was shown by further experimentation that inactivation of Iqgap1 in the mouse liver restricts the aggressiveness of HCC caused by Iqgap2 deficiency.

The findings of this study are reported in the March issue of Molecular and Cellular Biology.

Story first published: Wednesday, March 5, 2008, 12:32 [IST]