Of Meis and Men in the Middle

Meis proteins (brown) line glands in a normal prostate (left). In prostate cancer (right), they disappear.

Meis proteins (brown) are present in glands in a normal prostate (left). In prostate cancer (right), they disappear. Click to zoom in. Credit: H. Brechka.

Editor’s note: ScienceLife welcomes Hannah Brechka, graduate student in the Committee on Cancer Biology, who joins the team as a science communications intern through myCHOICE, a program that helps broaden experiences in scientific training at the University of Chicago. In her inaugural article, she describes her current research and the impact it could have on men with certain types of prostate cancer. 

Of Meis and Men in the Middle

When a man walks into the hospital and receives the diagnosis of prostate cancer, physicians have a crucial decision to make. Should they perform invasive surgery to remove the prostate? Or keep a close eye on the tumor in the hopes that it is the type that grows slowly?

Today, the answer depends on what the tumor looks like to a pathologist under a microscope. Some are easy to identify as aggressive, calling for equally aggressive treatment. Others may require treatment only after years of close surveillance by a doctor, or no intervention at all.

However, there are men in the middle. These men fall into an intermediate risk category, because it is difficult to predict whether their cancer will become aggressive or have little to no lethal potential. Physicians manage their care the best they can, but overtreatment of prostate cancer is a serious and potentially harmful problem for thousands of Americans every year. Surgically removing the prostate has risks including sexual impotence, urinary and bowel incontinence and, in some rare cases, death.

The goal of my research is to minimize that uncertainty for the men in the middle, by discovering novel molecular markers that predict aggressive disease in the intermediate risk population. And I think I’ve found one, called Meis.

Brechka4

Hannah in the lab

Meis proteins are essential for humans to develop normal blood vessels, limbs and organs. Classified as transcription co-factors, they bind and bring other proteins to the correct places in the genome for accurate gene expression. Meis’ are disrupted in cancers like leukemia, pancreatic, lung, colon and thyroid cancer. But they have never been investigated in prostate cancer, until now.

My lab and I have discovered that men with intermediate risk prostate cancers live more than three years longer if they have high levels of Meis expression. Those with low levels do not live as long.

This observation is just one piece on a long road towards developing a biomarker for predicting disease risk, and sparks many questions. In order to identify the mechanism by which Meis proteins provide this protection against aggressive disease, I work closely with surgeons and urologists from the University of Chicago Department of Surgery as a member of the lab of Donald Vander Griend, PhD, assistant professor of surgery and Director of Urologic Research.

I found that when I force cancer cells to overexpress Meis proteins, those cancer cells grow more slowly than the control group. By utilizing an array of human cancer cell lines and human tumor tissue, we have shown that healthy prostate tissue has higher levels of Meis than tumor tissue, consistent with our idea that Meis proteins act as tumor suppressors in the prostate.

Our hypothesis right now is that Meis proteins may help to keep cell proliferation controlled, in the same way that a traffic officer maintains a steady and controlled pace for cars on the street. If he leaves his post, the cars go faster, and start to crash into each other. The orderly system breaks down.

About one in seven American men will be diagnosed with prostate cancer in their lifetime, and one of them was my grandfather. I want my work to help make sure that prostate cancer becomes a disease men live with, not one that they die from.

About Hannah Brechka (5 Articles)
Hannah Brechka is a fourth year graduate student at the University of Chicago, and she studies prostate cancer in Dr. Vander Griend's lab. She's interested in how developmental mechanisms go awry in cancer cells. She's also an avid baker and enjoys brewing her own beer.
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