'Gateway' gene discovered for brain cancer

February 14, 2007

Researchers have discovered that the same genetic regulator that triggers growth of stem cells during brain development also plays a central role in the development of the lethal brain cancer malignant glioma. In experiments on mice with such gliomas, they showed that knocking out the function of a particular regulatory protein, Olig2, almost completely eliminated tumor formation.

The researchers said their findings suggest that targeting Olig2 could offer a potential avenue for treatment that would kill tumor cells without affecting normal tissue.

Dana-Farber Cancer Institute investigators Charles Stiles and David Rowitch and their colleagues reported their findings in the February 15, 2007 issue of the journal Neuron, published by Cell Press.

Olig2 is a "transcription factor"—a protein that regulates the activity of genes. Prior studies had indicated that it plays a central role in enabling neural stem cells to replicate during embryonic brain development. Also, studies have suggested that brain tumors might arise from aberrant neural stem cells or the neural progenitor cells to which they give rise.

Analyzing tissue from human gliomas, Stiles, Rowitch, and their colleagues discovered that Olig2 is activated in the stem and progenitor cells found in the tumors. In a mouse model of malignant glioma, they found that knocking out Olig2 function prevented tumor formation in 91 percent of the animals.

Their analysis of the role of Olig2 in both tumor cells and normal neural stem cells revealed that it plays a key role in enabling cell growth. Specifically, they found that Olig2 represses the gene for a cell-replication "brake" called p21, which normally inhibits cell growth. Thus, they concluded that Olig2 is a "unifying feature of normal cell cells and malignant glioma" and a "gateway" gene for brain tumor development.

"Lineage-restricted pathways that regulate brain tumor behavior may represent more specific therapeutic targets with little potential to affect off-target cell types," commented the researchers.

"Brain tumors remain a major cause of cancer-related death despite advances in surgery, imaging, and conventional treatment modalities," they wrote. "This emphasizes the need to develop novel medical strategies based on a comprehensive understanding of the biological mechanisms underlying gliomagenesis."

They wrote that "our findings identify this core transcriptional regulator as an important candidate for antitumor therapeutics." While transcription factors are not generally considered useful targets for anti-cancer drugs, there are multiple ways that Olig2 could be inhibited, as well as ways to target other components of the regulatory pathway by which it exerts its influence on tumor growth, wrote the researchers.

Source: Cell Press

Explore further: Experimental therapy halts treatment-resistant brain tumors

Related Stories

Experimental therapy halts treatment-resistant brain tumors

May 9, 2016

Researchers report in the journal Cancer Cell an experimental therapy that in laboratory tests on human cells and mouse models stops aggressive, treatment-resistant and deadly brain cancers called glioblastoma and high-grade ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Cow embryos reveal new type of chromosome chimera

May 27, 2016

I've often wondered what happens between the time an egg is fertilized and the time the ball of cells that it becomes nestles into the uterine lining. It's a period that we know very little about, a black box of developmental ...

Shaving time to test antidotes for nerve agents

February 29, 2016

Imagine you wanted to know how much energy it took to bike up a mountain, but couldn't finish the ride to the peak yourself. So, to get the total energy required, you and a team of friends strap energy meters to your bikes ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.