Gene Discovered that Inhibits Tumor Growth in Multiple Cancers

Published in the August 12, 2007, advance online publication of the journal Nature Medicine, the study found that a gene, HACE1, has the ability to help cells tackle various forms of stress, including environmental cancer triggers that cause tumor formation. When the HACE1 gene is missing or inactive, cancerous cells are able to form tumors, and when the gene is re-expressed, it prevents these cells from forming tumors.

The study was conducted in collaboration with Dr. Josef Penninger, from the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA; Vienna). "The discovery of this gene is very exciting because it clearly impacts a wide range of cancers, and provides a novel link between cellular stress and cancer,” stated Dr. Poul Sorensen, senior scientist at the BC Cancer Agency (Canada), an agency of the Canadian Provincial Health Services Authority. "If we can learn how to reactivate HACE1 or block cancer cells from inactivating this gene, it may be possible to improve treatments for many cancer patients.”

To assess whether HACE1 is a tumor-suppressor gene, researchers knocked out the gene in laboratory mice. They theorized that the mice would be more susceptible to tumor growth, and diverse tumors did indeed form but at a low rate. However, when the mice were also subjected to various forms of stress, including ultraviolet radiation, lung carcinogens, or other genetic changes, this resulted in a drastic increase in cancer growth, with the mice developing breast, lung, and liver cancers, as well as lymphomas, melanomas, and sarcomas.

Researchers also re-introduced the HACE1 gene into human tumor cells and discovered that cells lost their ability to form tumors. On the other hand, when levels of HACE1 were experimentally reduced in non-cancerous cells, they were able to form tumors. "We've always suspected that cancer is caused by a combination of genetic and environmental factors working together,” stated Dr. Sorensen. "Our results give us insight into how the disease takes root when a single gene is inactivated.”

The next phase of the research, according to the investigators, will be to evaluate the biologic mechanism that enables HACE1 to deal with cancer stress and block tumor formation.


Related Links:
BC Cancer Agency
Institute of Molecular Biotechnology of the Austrian Academy of Sciences