Biomedical Frontiers: Fall 1997, Vol.4, No.2
New Cancer Suppressor Gene Identified

Anti-tumor effect of mda-7 on the growth of human cervical carcinoma (HeLa) cells. Colony formation is reduced in cancer cells transfected with mda-7 expressing construct (RSV-MDA-7 Sense).

A newly identified gene that suppresses growth in human melanoma and other cancer cells holds promise as a ubiquitous suppressor of cancer.

In a paper published in the Aug. 20, 1996, issue of Proceedings of the National Academy of Sciences, CPMC researchers identified a melanoma differentiation-associated gene known as mda-7. The researchers found that the gene is expressed in normal melanocytes as well as in melanoma cells that have been chemically reverted to a more normal state. It is expressed in the early stages of melanoma (primary melanoma), but expression is reduced or absent in metastatic melanoma. More important, the study showed that mda-7 differentially inhibits the growth of melanoma and other tumor cells in culture, says Dr. Paul B. Fisher, senior author and professor of clinical pathology, director of neuro-oncology research, and the Chernow Research Scientist in pathology and urology at Columbia University.

The gene also inhibits growth of other types of cancer cells: The researchers tested mda-7 in various human cancer cells, including breast, central nervous system, cervix, colon, prostate, and connective tissue. In all cases, mda-7 inhibited colony formation. "This may indicate that mda-7 is a ubiquitous suppressor gene," says Dr. Fisher. "There have not been a large number of tumor suppressor genes identified--p53 is the most common one to date." Yet mda-7 may hold more promise than p53: The study found that mda-7 inhibited growth in human breast cancer cells, unlike transfection with wild-type p53 (mda-7 also worked in cells that did respond to wild-type p53). The gene did not affect growth of normal cells, including epithelial and fibroblast-derived cultures.

The next step in the research will be to identify and characterize genomic clones of mda-7 to determine if its structure is different in normal cells vs. cancerous cells. Additionally, recombinant adenoviruses expressing mda-7 will be used to test the effect of this cancer suppressor gene on tumor cell growth in vivo in nude mice containing human tumor xenografts. "This could eventually become a new treatment as well as a diagnostic for cancer," says Dr. Fisher.