Building on basics

Tackling Breast Cancer
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"That view has been challenged," Chen said. "The process is not that simple. It turns out that there are many, many more proteins involved."

In fact, Chen's lab recently discovered the role of a whole series of proteins, called co-activators, in the proliferation of prostate cancer. These co-activators are supposed to help the hormone receptor function. But in Chen's experiment these proteins became a little too helpful, overriding the hormone receptor. Chen's lab found that in prostate cancer cells, if you make the co-activators function in a hyper way, they will turn on the genes that directly control cell division.

"Those co-activators have a malfunction. They have higher activity than usual and this higher activity replaces normal function of hormone receptors," Chen said. "In a normal situation, or even in the primary stage of breast and prostate cancer, these proteins are just helpers. As the cancer progresses, those helpers become dominant. They are the main players in terms of telling the engine to turn on genes that regulate cell growth."

In other words, these co-activators may be culprits for relapse after hormone blockade therapy stops working. The clinical implications of this research are important, said Chen, who has funding from the U.S. Department of Defense and other sources.

"Cancer evolves by different mechanisms. Each patient has very different tumor cells. The mechanisms that cause a cancer can be very different," he explained. "If we can get the mechanisms clear, we can find a better way to directly target drugs. Our research opens another avenue for drug targeting.".

With rapidly improving technology, researchers can examine tumor samples for elevated co-activators. Researchers can use microarray chips, which allow them to look at all the genes expressed in a single cell at one time. They can also use immunohistochemistry, in which pathologists dissect the tumor into thin layers and stain the tissue with antibodies to highlight specific proteins.

In the future, researchers also may use gene therapy to turn off or decrease co-activator activities.

For the past several years, a key emphasis of the UC Davis Cancer Center has been to strengthen its basic science research program.

"All basic research has the potential to contribute to therapy, early detection or prevention," Kung said. "The reason the NCI wants to invest funds in teaching and research-oriented hospitals is that these facilities offer the best hope for moving basic findings to the bedside quickly. This is so essential in today's medicine."

Sophisticated image processing equipment is used to analyze gene expression in cancer cells.