Tumor Proliferation Gene Identified

Researchers have found that B-catenin activates the Nr-CAM gene, a gene that was thought to be expressed only in brain cells but is actually overexpressed in several types of cancer. They say the discovery may serve as a foundation for the development of new cancer drugs.

Introduction of Nr-CAM into cells that do not normally express this gene resulted in the enhanced ability of the cells to move spontaneously, and an improved ability to close artificial wounds, but also demonstrated a dangerous tendency for the cells to multiply rather than to stop proliferating. In addition, cells expressing Nr-CAM gained a new capacity to form tumors when injected into lab animals.

The investigators from the Weizmann Institute of Science (Rehovot, Israel) screened various types of cancers for evidence of Nr-CAM overexpression. They found that melanoma cells expressed a great deal of Nr-CAM, and that the quantity of Nr-CAM present in the cells correlated with the stage of the cancer's development.

The researchers injected human melanoma cells displaying different levels of Nr-CAM into mice and found a clear correlation between the presence of the protein and the ability to form rapidly growing tumors. In addition, they were able to arrest the movement of melanoma cells in culture by adding an antibody that blocked the extracellular portion of the Nr-CAM molecule.

From these data, Professor Avri Ben-Ze'ev, of the Weizmann Institute's department of molecular cell biology, concluded that Nr-CAM, a molecule not previously known to play a role in the development of cancer, is a target gene induced by B-catenin to promote uncontrolled cell proliferation.

"Since B-catenin is hyperactive to different degrees in almost every type of cancer, the discovery of Nr-CAM as a target for suppressing these cancers is very promising,” Professor Ben-Ze'ev said. "We were especially excited when we could demonstrate its potential relevance to some of the most prevalent types of cancer in the Western world--melanoma and colon carcinoma.”




Related Links:
Weizmann Inst.