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Skin cancer study uncovers new tumor suppressor gene
Date:3/29/2009

e tumor samples. Nearly one-quarter of the tumors analyzed had at least one MMP gene mutation. Some mutations were found in as few as 3 percent of tumors, while more than 6 percent of tumors had mutations in MMP-8 and more than 7 percent had mutations in MMP-27, which codes for an enzyme very similar to MMP-8.

"We often talk about cancer as though it is one disease, and cancers do have many common denominators. But when we look at the DNA level, we see that different cancers have different genetic profiles, and so do different patients who have the same cancer," said the study's senior author, Yardena Samuels, Ph.D., an investigator in the Cancer Genetics Branch of the NHGRI's Division of Intramural Research.

Dr. Samuels and her collaborators followed up their DNA sequencing work with cell and animal studies to see whether MMP-8 mutations affect enzyme function. Strikingly, the researchers showed that five of the mutations reduced activity of the MMP-8 enzyme. The researchers next studied whether MMP-8 mutations promote activities related to cancer. Indeed, cells with MMP-8 mutations showed increased ability to multiply outside the constraints of normal cells, a hallmark of cancer development known as anchorage-independent growth. Likewise, cells with MMP-8 mutations had a greater ability to migrate -- a key aspect of cancer metastasis -- than normal cells.

The researchers found that mice injected with cells expressing normal MMP-8 did not develop skin ulcers, which are one of the most important measures of cancer aggression in melanoma. In contrast, mice injected with cells expressing mutated MMP-8 went on to develop ulcerations and metastases in their lungs.


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Contact: Raymond MacDougall
macdougallr@mail.nih.gov
301-402-0911
NIH/National Human Genome Research Institute
Source:Eurekalert

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