LOS ANGELES -- A scientist at Cedars-Sinai Medical Center has discovered a gene that exists in malignant tumors of the brain, liver, breast, colon, kidney, and reproductive organs, but not in healthy adults, stirring hopes that a vital key to cancer development and progression may have been unmasked.
Julia Y. Ljubimova, M.D., Ph.D., a cancer researcher in the Maxine Dunitz Neurosurgical Institute at Cedars-Sinai Medical Center, announced the discovery of a novel human malignancy-associated gene (MAG) in the October issue of Cancer Research, the Philadelphia-based journal of the American Association for Cancer Research.
"We feel that this gene may 'turn on' the process of malignancy," said Dr. Ljubimova (pronounced "Lou-bee-mo-va"), a native of Russia who is a member of Dr. Keith Black's neurosurgical research team. Once the newly-found gene has been completely sequenced, a process that could be completed in three months, work will begin on genetically engineering a method of blocking the gene's expression. Herein may lie its greatest clinical significance, said Dr. Ljubimova. "Most patients die from metastasis or invasion," she said. "If, using antisense technology, the gene could be deactivated, a tumor cell's blueprint for rampant growth might be destroyed, and the cancer stopped before it spread."
"The discovery of the MAG gene was serendipitous," Dr. Ljubimova explained, "the result of looking at expression of another gene (c-met proto-oncogene) in normal and cancerous human liver tissues. An extra polymerase chain reaction (PCR) band kept appearing in specimens from livers from patients with advanced cirrhosis or liver cancer. Further exploration led to the conclusion that it was a gene associated with malignancy. In her paper, Dr. Ljubimova wrote, "Analysis of 30 liver and five brain disease cases for MAG expression has indicated its potential importance in liver and brain neoplasia. The absence of MAG expression in different normal tissues and its presence in various malignancies supports the hypothesis that this novel gene may play an important role in the process of malignant transformation."
The MAG gene is not the only example of a genetic signal present in more than one type of cancer. Expression of prostate specific antigen, for example, is observed in both prostate and breast cancer.
MAG, however, appears to be a common element in a wide variety of cancers. It was seen in 90 percent of 51 premalignant and malignant tissue samples, including glioblastomas and carcinomas of the lung, breast, colon, kidney, prostate, endometrium, ovary, and uterus. Intriguingly, expression of MAG messenger RNA (mRNA) was also found in fetal brain and liver tissue. Under normal circumstances, the gene is no longer seen once organs mature, and no evidence of its telltale polymerase chain reaction band could be found in any tissue from a healthy adult. Expression of this gene was supported by other molecular biological methods.
Another so-called oncofetal gene is alpha-fetoprotein, which is found in embryonic liver tissue and in liver cancer (hepatocellular carcinoma), but not in normal adult liver cells. It is believed that these genes give commands for rapid growth that are appropriate in a developing fetus, but dangerous in an adult whose cells should divide in a slow and orderly fashion.
Expression of the MAG gene appeared in tissue samples of patients with advanced cirrhosis of the liver, a condition that often precedes liver cancer, but not in samples from patients with a liver disease that is not associated with malignancy, fulminant hepatic failure. This suggests the MAG gene is not just a marker for disease, but an early player in the transformation of cells from normal to malignant.
Dr. Ljubimova noted that the Cedars-Sinai work was an interdisciplinary effort between the Maxine Dunitz Neurosurgical Institute, led by Dr. Keith Black; the Department of Surgery, led by Dr. Achilles A. Demetriou; and the Department of Pathology, led by Dr. Stephen A. Geller.
Dr. Ljubimova is available for interviews. To arrange, please contact Roberta
Nichols
at (310) 855-4767.
Media Contact: Roberta Nichols or Anita Roark (310) 855-4767
Journal
Cancer Research