Protein Identified That Controls Brain Tumor Cells

"It is very powerful and may be an attractive target for anti-cancer therapy.”

The protein is also involved in late-stage skin, breast, colon, and thyroid cancers, which may suggest possible treatment options for many cancers. Dr. Debinski and coworkers have located the protein while studying glioblastomas, the most frequent type of brain tumor. Glioblastomas are thought to be the least curable of all human cancers. Similar to other tumors, glioblastomas need their own blood supply to grow and metastasize. The scientists' first goal was to determine what controls this mechanism.

However, when they measured the protein levels that they believed might be involved, they discovered only very low levels. Instead, they found that a little-known protein, called Fra 1, is present in large amounts in the tumor cells. "We were very surprised when we saw it for the first time,” said Dr. Debinski. "We had to learn more about Fra-1 because it is not a widely-studied biological factor.”

What they found out about this protein is that it is able to regulate a set of different genes because it is also a transcription factor, meaning it "reads” the genetic material in cells. Transcription factors help control whether the instructions of genes are carried out by the cells. The researchers performed several studies to understand more about Fra-1's role in glioblastoma formation. They discovered that it makes the tumor cells more elongated, which might make it easier for them to infiltrate normal tissue. It also enables tumors to grow a blood supply. Also, when nontumor-forming cells were supplied with Fra-1, they started to produce tumors. But when this protein was eliminated from cells that were already tumor-producing, they stopped forming tumors.

"It is a powerful biological factor,” Dr. Debinski remarked. In this study, the investigators discovered that more than 50 different genes appear to be affected by Fra-1, suggesting that its effects may be even broader than this initial study demonstrated. "We believe it may be good target for anti-cancer therapy, but we need to explore more.”

The scientists suspect that Fra-1 functions by cooperating with other molecules. If it proves difficult to control the actions of Fra-1 with drug therapy, one of these other molecules might be more susceptible to treatment. "Even if Fra-1 it not the ideal treatment target, I believe we're on the right track to identify one,” stated Dr. Debinski.

The study was published in the April 2005 issue of the journal Molecular Cancer Research.



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