by Cindy Abole, Public Relations

Dr. Daniel J. Fernandes, left, professor and interim chairman of the Department of Experimental Oncology, and Dr. Steve Frawley, professor and director of MUSC's Laboratory of Molecular Dynamics, with some of the equipment purchased with the grant money.

Borrowing from glow-in-the-dark chemistry in fireflies, MUSC researchers have developed new techniques to understand the effects of gene activity within breast cancer cells. They expect the process could lead to development of a test that accurately predicts the most effective anti-cancer treatment.

"The process allows us to look at what's happening inside an individual cell over a course of time," said Daniel J. Fernandes, Ph.D., professor and interim chairman of the Department of Experimental Oncology. He, with Steve Frawley, Ph.D., professor and director of MUSC's Laboratory of Molecular Dynamics within the Department of Cell Biology and Anatomy, and a number of Hollings Cancer Center scientists were able to secure funding for equipment needed to measure gene expression in living cells on a cell-by-cell basis.

The National Cancer Institute awarded them a grant of $302,000, and they received an additional $60,000 from the Hollings Cancer Center.

The new equipment is actually a photon (a unit of light energy) capture and amplification system that complements an existing system currently funded by grants to the Frawley group from the National Institutes of Health and the National Science Foundation. With this equipment, Frawley group is able to detect gene activity by using natural bioluminescence, light produced by a chemical reaction between the enzyme luciferase and an energy-rich chemical called luciferin within an organism. It's a similar luciferase-luciferin reaction that produces the light from fireflies.

Here's how the Frawley group does it:

They inject cells with DNA molecules engineered so that the regulatory portion of a gene in each DNA molecule controls the luciferase-producing activity of the gene. (Genes in the DNA molecule are the basic physical and functional units of heredity.) That way, researchers have a "reporter gene," a gene that encodes an easily measured protein—in this case, luciferase—to test the ability of a stimulus to turn on that gene.

When a gene is turned on, it's called "gene expression," a term that describes a gene in its active state. In the DNA of cells, not all genes are constantly active. There are some 100,000 genes in the human genome. Some are activated (expressed) frequently. Some are almost never turned on.

The activation of the regulatory sequences of that altered gene leads to the production of the "reporter" gene (luciferase), which induces the cell to "twinkle" in tandem with an unaltered gene. The rate of "twinkling" is measured with the new ultra-sensitive cameras and data collection software acquired through the grants. The system provides a real-time read-out for the activity of the endogenous (unaltered) genes to which the fused, regulatory sequences correspond.

Related research

Frawley's team has published several papers studying prolactin gene expression in pituitary lactotrope cells, which secrete the hormone prolactin. Prolactin plays a major part in breast development and in a woman's milk production after she gives birth. Studies are also under way with pituitary cells that secrete growth hormone and with neurons, which produce gonadotropin-releasing hormone. This is the hypothalmic peptide from the brain that controls reproductive function.

Their current work with breast cancer cells is supported in part by a Department of Energy Environmental Hazards Assessment Program (EHAP) grant to MUSC. Staffers conducting the work are headed by Scott Willard, Ph.D., a research fellow in Frawley's group.

The work centers around the effects of estrogen (natural, environmental or pollutant) on the progression of breast cancer and features two components: The first is aimed at obtaining a basic understanding of how estrogen regulates cancer genes. The other is more clinically relevant in nature and deals with the controversial breast cancer drug Tamoxifen. This drug prevents estrogen-dependent growth in breast cancer cells.

Using the technology

When a cancerous breast tumor is removed, physicians measure receptors within the cells that bind to estrogen. If they are present, the patient can be treated with Tamoxifen. Problems arise because not all estrogen receptors are responsive to the anti-estrogen drug. Thus, some patients treated with the drug may not benefit from it.

The new technology allows Frawley's group to develop a test in which a patient's own tumor cells will be used to predict their possible responsiveness Tamoxifen.

"Hopefully, refinement of this technology will enable us to evaluate the responsiveness of multiple genes to a battery of therapeutic agents," Frawley said. "By tailoring treatment to each patient's tumor profile, the surgeon/oncologist should be even more effective in treating the disease."

"This unique partnership serves as a model of collaboration between the Hollings Cancer Center and other academic departments doing research in cancer," Fernandes said. "It has all the right potential to meet research goals for the Hollings Cancer Center and MUSC."