Endeavors - Firefly Mice

Could glowing rodents come to the aid of cancer researchers … and patients?

Why would a researcher put a firefly gene in a mouse? To make it glow, of course. Why would a researcher want to make a mouse glow? To study how it ages and how cancer cells develop, of course.

Ned Sharpless, a geneticist at UNC’s Lineberger Comprehensive Cancer Center, researches the role of a protein called p16 in aging and cancer.

We humans typically have more p16 in certain cell lines in certain parts of our bodies. In some cells, p16 increases a lot as we age. And that’s good because p16 is a tumor suppressor.

Here’s how we explained it in a 2011 Endeavors feature:

When a carcinogen such as cigarette smoke enters the body, it can damage cells and alter DNA “Say you have ten cells with equal risk of becoming cancer,” Sharpless says. “Eight cells take in a carcinogen, but not enough of it, and spit it out. Nothing happens to those cells; their p16 stays the same. One of the cells takes in the carcinogen, is really damaged, and p16 is activated. P16 stops that cell from dividing. It’s in jail, never to be heard from again.” The tumor suppressor is working, and p16 increases manyfold.

So pharmaceutical companies developed drugs that mimic p16 with the hope they’d crush cancer cells. But the drugs offered lackluster results. Sharpless found out why.

In the above example, cigarette smoke does not damage eight cells. It does damage a ninth cell, but p16 activates and stops the cell from dividing. But with that tenth cell, there’s a problem, Sharpless tells us:

“That tenth cell takes in the carcinogen and DNA is damaged, but p16 is not activated for one of two reasons—the DNA damage is not the kind that activates p16, or the carcinogen mutates the p16 gene so that the protein is not induced. In either event, that cell is significantly damaged and well on its way to becoming cancer.”

So p16 drugs don’t work as well as scientists had hoped. But while Sharpless was conducting that research, his lab created a way to measure the level of p16 in T cells. This could help doctors pinpoint a person’s molecular age, which would help doctors determine how patients would handle specific treatments or procedures. Also, he found that the p16 drugs protected mice from the ravages of radiation and chemotherapy.

Now, Sharpless has found another way to exploit the relevance of p16.

His lab genetically engineered mice so that when they begin to express p16, they start to glow, which is barely visible without a special type of camera. The mice glow more as they age, and they glow even more when p16 goes into overdrive while trying to stop cells from dividing.

This means that the mice began glowing just as cancer was starting to develop.

If Sharpless had tried to detect cancer in the mice with traditional methods, he would’ve had to wait 100 days. That’s an astounding time difference, considering how important early detection is for cancer patients.

Here’s the upshot: no one will make humans glow—at least Sharpless won’t—but there could be a day when a doctor measures the amount of p16 in the T cells of a patient. The measurement could be part of an early detection system. Treatments could be used to battle cancer cells before they form the sorts of tumors that are hardest to destroy.

Ned Sharpless is a professor of medicine and genetics in the School of Medicine and the Wellcome Distinguished Professor of Cancer Research and Deputy Director at the Lineberger Comprehensive Cancer Center.

To read more from Endeavors, visit their website.

Date: March 1, 2013