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Molecular Complexity
Researcher explores the molecular by JANE M. SANDERS | |
IN BREAST AND OTHER types of cancer, genes that encode the cytochrome P450 family of enzymes are overexpressed, creating an overproduction of these proteins.
Assistant Professor of Biology Marion Sewer studies the genes that encode a subset of cytochrome P450 enzymes that make steroid hormones such as estrogen. Her research team included recent graduate Houman Khalili, pictured here. (300-dpi JPEG version - 846k)
Georgia Tech Assistant Professor of Biology Marion Sewer studies the genes that encode a subset of cytochrome P450 enzymes that make steroid hormones such as estrogen, testosterone and cortisol (the “stress” hormone). Sewer primarily investigates the molecular events that turn on these genes in response to chronic stresses.
“This research is complex at the molecular level in terms of the steps involved in turning on genes, given all the proteins and pathways that are involved,” Sewer notes.
But Sewer is now extending this basic research to studies of cancers that are “hormone dependent” – that is, their progression is linked to an overproduction of hormones.
In breast cancer, the current treatment is a chemotherapy drug called Taxol (model of a Taxol molecule shown here), which inhibits the ability of estrogen to turn on genes. A more effective treatment in the future may be to combine Taxol with an agent that inhibits estrogen production in the breast only.
In breast cancer, the current treatment is a chemotherapy drug called Taxol, which inhibits the ability of estrogen to turn on other genes. A more effective treatment in the future may be to combine Taxol with an agent that inhibits estrogen production in the breast only, Sewer notes. Her research could contribute to the development of such a drug, she adds.
But Sewer must first conduct more basic research on the P450 gene that converts estrogen to a toxic compound that binds to DNA and leads to cancer. This particular gene is overexpressed in more than 95 percent of cancerous breast tissue. Though this gene has a documented role in causing other cancers – including stomach cancer and smoking-related lung cancer – its function is not clearly understood in breast cancer, Sewer says. If her research team can learn why this gene is turned on at such a high level, then they might be able to identify a way to turn it off in the breast.
At this stage in their research, Sewer and her team of six undergraduate and graduate students are characterizing different regions of this gene and how those regions affect expression.
She estimates that it will be at least 15 years before her research would lead to human trials of potential pharmaceutical agent that might be developed from her team’s findings.
Under normal conditions, cytochrome P450s perform a variety of functions – from ridding the body of toxic compounds such air pollutants and pharmaceutical drugs to producing essential biological molecules, such as cholesterol and hormones.
photo by Gary Meek
For example, estrogen is overproduced in breast cancer, and testosterone is overproduced in prostate cancer. This expanded research program was funded in 2003 with a five-year grant from the Georgia Cancer Coalition.
courtesy National Cancer Inst.
For more information, contact Marion Sewer at 404-385-4211 or marion.sewer@biology.gatech.edu.
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Last updated: July 7, 2004
