DLC1 is another anti–oncogene

Scientists at Cold Spring Harbor Laboratory have proven that the DLC1 gene is a suppressor of tumor growth. In experiments on live mice, they demonstrated that its deletion, inactivation or absence accelerates events leading to the development of an aggressive form of liver cancer similar to human hepatic cell carcinoma.

Tumor suppressor genes, or anti-oncogenes (or rather, not the genes themselves, but the proteins encoded by them) perform important functions in the work of intercellular interaction systems that prevent uncontrolled cell growth and proliferation. These genes can be inactivated through various DNA damages, including deletions, mutations and so-called epigenetic changes in the chemical configuration of DNA.

The absence of the region of the 8th chromosome, in which the DLC1 gene is located (the name is an abbreviation of the initially assumed role of the gene "deleted in liver cancer", "deleted in liver cancer"), was previously registered in mammalian liver cancer cells. The studied region of the chromosome is quite large and theoretically may contain several anti-oncogenes. The authors decided, if possible, to obtain convincing evidence that the DLC1 gene is a suppressor of tumor growth and demonstrate at the molecular level that its absence leads to cellular pathology, the result of which is the development of liver cancer. It turned out to be interesting that the absence of DLC1 is observed in a number of epithelial tumors, which indicates its possible role in the development of many types of cancer.

To obtain evidence of the role of DLC1, scientists used genetic engineering methods to block the expression of the DLC1 gene in normal mouse liver cells. In almost all cases, the introduction of such cells into the liver of healthy mice led to the development of cancer, and the introduction of a normal copy of the gene into the cells stopped the growth of the tumor. However, the reason for the formation of tumors is not the absence of a gene as such. The authors demonstrated that an abnormally low concentration or complete absence of the protein encoded by it triggers complex cascades of events. The DLC1 protein belongs to the family of enzymes of small Rho-GTPases, which are so-called "molecular switches".

Using RNA interference, the researchers effectively "turned on" and "turned off" the activity of the DLC1 gene in living cells, which allowed them to isolate the intermediate compound RhoA, the presence of which is a necessary and sufficient condition for starting uncontrolled cell division. The absence of DLC1 in the cell activates RhoA, inducing tumor formation. In separate experiments, knockout of the DLC1 gene and activation of RhoA synthesis led to the same result – the development of liver cancer.

These results point to potential preventive and therapeutic targets for fighting liver cancer, and possibly other types of cancer.

Article by Xue et al. "DLC1 is a chromosome 8p tumor suppressor whose loss promotes hepatocellular carcinoma" published in the journal Genes & Development.

Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily

10.06.2008