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Israelis find key to containing cancer

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Wednesday, June 1st, 2011

As reported in Israel21c:

It is called simply p53, a short name that belies its starring role in halting the spread of cancer.

Israeli scientists already knew that when it is activated, the p53 gene produces a protein that can halt and even kill cancerous cells. Now, a team headed by Prof. Yinon Ben-Neriah and Dr. Eli Pikarsky of the Institute for Medical Research Israel-Canada at the Hebrew University of Jerusalem have discovered that p53 also governs a mechanism that keeps those deadly cells from invading healthy epithelial tissue lining the cavities and surfaces of many internal organs.

As the researchers described in the February issue of the journal Nature, the ability to “turn on” p53 could be a critical means of protection against colorectal and other epithelial forms of cancer.

Engineered mice yield surprising discovery

Building on earlier p53 studies by Dr. Moshe Oren of the Weizmann Institute of Science, who joined the current research team, Hebrew University doctoral students Ela Elyada and Ariel Pribluda spent six painstaking years engineering a unique mouse model to study the effect of p53 on the cell-invasion process.

“53 has been known for 20-something years as a gene that protects against cancer by suppressing tumors,” Ben-Neriah explains to ISRAEL21c. “It has several mechanisms to do this, and you can observe these phenomena even in a tissue culture dish.”

But his team wanted to go deeper. After developing a model that mimics colorectal cancer in mice and removing their p53 gene, the researchers saw something never before observed: malignant cells began invading neighboring cells at a fast clip.

“One of the earliest signs of cancer progression is this invasion process,” says Ben-Neriah. “Normally, it is slow. In humans, it takes 10 to 15 years for colorectal cancer to develop. Even in mouse models, it takes at least six months. But when we knocked out 53, we started observing the malignant process within seven days, and it happens throughout the gut. There was something fundamental going on that had to do with 53.”

Using sophisticated tools to analyze DNA and gene expression, the researchers found specific genes that kick off the invasion process. And when p53 is activated, it keeps those invasion-activating genes in check.

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