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New tumor suppressor may play important role in deadly brain tumors

Researchers from Massachusetts General Hospital (MGH) have identified a new tumor suppressor gene that appears to be inactivated in gliomas, a deadly form of brain tumor. Levels of the protein coded by the gene, called ING4, appear to correspond with tumor aggressiveness, with the lowest levels seen in the highly malignant glioblastomas. In their report in the March 18 issue of Nature, the researchers also describe how ING4 appears to suppress the growth of new blood vessels to feed the tumor, a process called angiogenesis.

ING (for INhibitor of tumor Growth) is a family of proteins known to be essential to the activity of the powerful tumor suppressor p53. The research team, led by Igor Garkavtsev, MD, PhD, of the Steele Laboratory in the MGH Department of Radiation Oncology, searched a gene database to identify genes with a similar structure to the previously identified ING1.

"The ING4 gene had been cloned simultaneously in both laboratories at the MGH and at the National Institutes of Health," says Garkavtsev. "Its functional role in the prevention of tumor progression had not been investigated. When we found that malignant gliomas have strikingly lower levels of ING4 and knowing that ING4 regulates angiogenesis, this sparked interest toward potential targets that were independent of p53."

The research team first tested samples from 50 tumors of various malignancy grades for evidence of ING4 gene expression. They found that gene expression was two to three times lower than normal in lower-grade tumors and up to six times lower in the high-grade glioblastomas. Similarly another test that compared tissue from brain tumors with samples of nearby normal tissue found abundant ING4 levels in the normal tissue but significantly less in the tumors.

To investigate the protein's effect on angiogenesis, the researchers created lines of tumor cells that were manipulated to express levels of ING4 higher and lower than found in control
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Contact: Julie Bergan
jbergan@partners.org
617-726-0274
Massachusetts General Hospital
22-Mar-2004


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