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Metastasis suppressor gene identified

transfecting T24T cells with RhoGD12 and injecting them into immunocompromised mice, they established that RhoGD12 is causall

Last Updated: 2002-11-15 12:43:11 -0400 (Reuters Health)

NEW YORK (Reuters Health) - A newly identified gene, RhoGD12, suppresses the growth and metastasis of a wide variety of human cancers, investigators at the University of Virginia Health Sciences Center in Charlottesville report.

According to their paper in the November 15th issue of Cancer Research, RhoGD12 is the only gene whose expression levels were associated with both tumor grade and stage in DNA microarray analysis of 105 primary human tumors.

Dr. Dan Theodorescu and his associates began their research by evaluating gene expression profiles of a human bladder cancer cell line (T24) and an aggressive isogenic variant with high metastatic ability (T24T). There were 2368 genes whose expression correlated with reduced invasiveness and metastasis.

They followed this work by analyzing gene expression profiles of human carcinomas from the lung, prostate, breast, colon and rectum, kidney, bladder and liver. With the participation of Novartis, the researchers used the best microarray analysis currently available, Dr. Theodorescu said. It was in this analysis that they identified RhoGD12 as the "only gene that tracked with stage and grade in the human tumors," he told Reuters Health.


In the latter group of mice, the transfected gene may have "pushed the cancer back to its natural scenario," vastly diminishing but not entirely eradicating the ability for secondary spread, "or else the gene construct may have been suppressed completely in some cells," Dr. Theodorescu suggested.

He also said tissue culture findings established that RhoGD12 blocks invasion by inhibiting cell motility.

The Virginia researchers hope that RhoGD12 can be used as a marker to distinguish lesions with high metastatic capacity from those that will remain indolent. RhoGD12 also represents "a promising target for therapy," they add.

According to Dr. Theodorescu, the next step is to find out exactly what the targets of the gene RhoGD12 are, and if they can be manipulated and blocked.

"We now have good leads on what the mechanism of RhoGD12 is, so we're pretty excited," he added.

Cancer Res 2002;62:00-00.

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