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P&S Journal

P&S Journal: Winter 1998, Vol.18, No.1
Research Reports
A Master Switch for Cancer Aggressiveness?

Scientists have discovered a gene that makes a cancer cell more aggressive and likely to metastasize. The gene, PEGen-3 (for Progression Elevated Gene 3), appears to act as a "master switch" for cancer aggressiveness and metastasis and may represent a new class of genes that regulate cancer growth. The study was published in the Aug. 19, 1997, issue of Proceedings of the National Academy of Sciences.

PEGen-3 doesn't change a normal cell into a cancerous one, says Dr. Paul B. Fisher, senior author and professor of clinical pathology, director of neuro-oncology research, and the Chernow Research Scientist in neurosurgery, pathology, and urology. Instead, it affects existing tumor cells by directly facilitating traits that increase their progression and aggressiveness.

PEGen-3 has potential for therapeutic use if its presence or absence can eventually be used to predict whether a cancer will be aggressive. The gene also could serve as a target for genetic therapy for cancer. PEGen-3 is similar to another set of genes (gadd34 and Myd116) that have already been found to be involved in DNA damage and differentiation pathways.

Researchers identified and cloned the gene using a modified and efficient subtraction hybridization scheme, a method pioneered and patented by Dr. Fisher at Columbia in 1993. When the researchers placed PEGen-3 in cancer cells and injected them into animal models, the result was rapid production of larger and more aggressive tumors compared with animals injected with the same tumor cell line not expressing PEGene-3. The scientists also studied the native expression of PEGen-3 as a function of cancer progression by placing suppressed cancer cells containing a Ha-ras oncogene and a Krev-1 ras-suppressor gene in animals. The suppressed cells formed tumors and metastasized after long periods of time. Unlike the suppressed cancer cells, which did not express PEGen-3, the tumors expressed the gene and the metastases expressed even more PEGen-3. These observations suggest the intriguing and testable hypothesis that PEGen-3 expression may mediate the escape from tumor suppression and the reacquisition of oncogenic potential in suppressed tumor cells. In this context, PEGen-3 may act as a master switch that allows tumors to grow more rapidly and aggressively.

The study was funded by the National Cancer Institute, the Samuel Waxman Cancer Foundation, and the Chernow Endowment. Other authors of the paper were Drs. Zao-Zhong Su and Yijie Shi.

copyright ©, Columbia-Presbyterian Medical Center

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