P&S Journal: Fall 1994, Vol.14, No.3
Columbia scientists have identified six novel genes involved in a process that changes melanoma cells and other cancer cells in culture into cells that lose their cancerous properties. The results could lead to a better understanding of how healthy cells progress to melanoma and other cancers and to the development of cancer drug screening assays and improved diagnostic tests for such cancers. These genes also could prove useful as part of genetic-based therapeutic strategies for the treatment of melanoma and other cancers.
Dr. Paul B. Fisher, professor of clinical pathology, discussed his findings on the novel genes at a spring meeting of the American Association for Cancer Research.
The six novel genes were found through a process called subtraction hybridization, a method (Columbia patent pending) to isolate differentially expressed genes developed by Dr. Fisher and his laboratory. They treated melanoma cells in culture with recombinant beta interferon and mezerein to induce the malignant cells to lose growth potential and to mature to a benign stage in their development, a process called terminal cell differentiation. Cancer can develop when, for various reasons, cells return to an earlier stage in their development and grow uncontrollably.
When the treated melanoma cells differentiated they stopped growing uncontrollably and expressed the six novel genes Dr. Fisher calls melanoma differentiation associated genes. Expression is the creation of a gene's messenger RNA, a molecule that allows the cell to take the information contained within a gene and manufacture proteins, the workhorses of cells.
As would be expected if these genes presumably function to keep cells under normal growth control, the genes are expressed in healthy melanocytes, skin cells Dr. Fisher found. But since melanoma, like other cancers, is a progressive disease leading to a loss of cellular growth control, Dr. Fisher found that the expression of these genes decreased in cancer cell lines-including melanoma, lymphoma, promyelocytic leukemia, neuroblastoma, and brain cancer glioblastoma multiforme lines-as the cancer became more advanced.
Dr. Fisher is continuing to characterize these six novel genes to determine their roles in melanoma and other cancers.
"Since the different genes are expressed at different stages in the progression of the cancer," said Dr. Fisher, "they may prove to be good diagnostic and prognostic markers that determine the stage of advancement of melanoma and other cancers." Studies to correlate gene expression and cancer stage are under way.
Additionally, Dr. Fisher said, "the novel genes display discrete patterns of expression depending on the inducing agent." Thus, differential gene expression can be used as a way to screen for new anti-cancer agents that induce differentiation, growth suppression, or DNA damage. Screening experiments are ongoing, and the researchers are exploring genes' potential in gene-based therapeutics.
Dr. Fisher's research is supported by grants from the National Cancer Institute, the National Institute of General Medical Sciences, the Chernow Endowment, and the Samuel Waxman Cancer Foundation.
- Robin Eisner