Although science has made much progress in understanding why cancer occurs—smoking, diet, environmental pollutants, viruses—the mechanisms of cancer are still elusive. Nancy Magnuson, of the School of Molecular Biosciences, has been studying an enigmatic gene called Pim-1 since 1988.

The questions I would most like to know the answers to are, “What is the normal function of the proto-oncogene called Pim-1, and how does Pim-1’s function contribute to the production of cancer?”

Although Pim-1 has long been known to be involved in cancer production, it has never been demonstrated how this occurs. Importantly, Pim-1 is only found in certain types of cells, and these are the cells that most often become cancerous as individuals grow older. Pim-1 protein is found at high levels in these cells, and we think that this is most likely a normal situation. Furthermore, there is compelling evidence—but not proof—that the normal function of Pim-1 is to promote cell survival. In general, this is an important and healthy function. However, when a cell undergoes a mutation, for example from an environmental carcinogen, the presence of Pim-1 may inadvertently protect the mutated cell from dying by a pathway designed to delete defective cells. Because the defective cell is able to survive, it continues to pick up further mutations over time and grows more and more out of control. And we know that accumulation of mutations leads to the generation of lethal metastatic cancer.

—Nancy Magnuson
Microbiology; Molecular Biosciences

How big a deal is Pim-1?

Magnuson believes that Pim-1 is probably involved in all carcinomas, the most common cancers. Carcinomas arise from epithelial tissues, such as skin and the linings of body cavities, and glandular tissues such as the breast and prostate gland.

So does Pim-1 cause cancer?

No, says Magnuson. Rather, in combination with other factors, it seems to predispose cells to cancer.

What exactly is cancer?

No, that’s not a dumb question. There is no one disease called “cancer.” But in general, cancer is the new growth of tissue that results from rapid and uncontrolled production of abnormal cells. And we’re far from understanding exactly how it occurs.

Why does Pim-1 turn bad?

It doesn’t really. It seems to just be doing its job of helping cells survive. And it seems that the gene does not distinguish between good and bad, or normal and cancerous cells. In fact, Magnuson believes that Pim-1 normally inhibits apoptosis, or programmed cell death, through which the potentially lethal cell would die once its usefulness had passed. Inhibiting apoptosis in a cancerous cell, obviously, is not good.

How does a normal cell become cancerous?

One does not just come down with cancer, says Magnuson. Rather, cancer seems to be a complex process that may stretch over years. There probably is no single cause. Rather, a chance mutation in a cell may in turn cause increased expression of proteins by other genes that stimulate growth in yet more genes. As the cells increase in number, so does the chance for mutation. So cancer is the sum of many events.

With hundreds of millions of dollars spent fighting cancer, why hasn’t anyone come up with a magic bullet?

Mainly because there is no convenient target, says Magnuson. Cancer is not like a cavity. You can’t just pull the cancerous tooth. Cancer is a process. In fact, often when cancer is targeted locally, it comes back later with a vengeance. As bacteria develop resistance to antibiotics, so malignant cells can adapt and become tougher.

Take-home message:

Although there is no simple cure on the research horizon, scientists have made impressive progress in understanding a class of diseases that is far more complicated than anyone imagined even a few years ago.