Sp2 is a member of the Sp family of transcription factors, proteins that act as cellular “switchboard operators” by turning genes on or off as needed. The scientists, with the Center for Comparative Medicine and Translational Research (CCMTR), had noted that the development of skin tumors was correlated with the production of too much Sp2, and others had noted similar findings in prostate cancers, but beyond that very little was known about the protein.
Dr. Jonathan Horowitz, an associate professor of oncology in the Department of Molecular Biomedical Sciences, and CCMTR colleagues Dr. Jeffrey Yoder, Jianzhen Xie, Haifeng Yin, and Teresa Nichols, wondered whether they could use over-production of Sp2 in tumors as an early indicator of tumor formation. They inserted a fluorescent marker into zebrafish—attached to the Sp2 gene—allowing them to trace the synthesis of Sp2 throughout the organism. When the zebrafish were viewed under ultraviolet light, the Sp2 marker glowed red where the gene was expressed.
“Zebrafish are good model animals for this research because their embryos develop in a 24-hour period, and they develop externally so you can watch what is happening under a microscope,”
According to Dr. Horowitz, earlier findings had suggested that Sp2 regulated development—
“We noticed that in the adult zebrafish that carried the fluorescent marker, the ‘lights were out’ except in the ovaries of the females, which glowed bright red,” Dr. Horowitz says. “Then when the female laid her eggs they also glowed red. This told us that Sp2 must be important for the earliest stages of development. Sure enough, if we eliminated Sp2 in an embryo the embryo simply didn’t develop. We think that we’ve uncovered a fundamental mechanism for embryonic development.”
The CCMTR team’s findings will appear in the February 2010 issue of the Journal of Biological Chemistry.
Dr. Horowitz believes that the fluorescent fish will help him answer another question about Sp2: whether the protein plays a role in the development of certain types of cancer.
“If Sp2 is important in the development of brain cancer, for example, and you’re using our fluorescent zebrafish to study brain tumors, then theoretically as the tumor grows you should see a bright red brain when you look at those fish under ultraviolet light,” Dr. Horowitz says. “We think that these fish may be a useful tool—an aquatic canary in the coal mine—that will allow us to detect early tumor development.”
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