Gene B-myb essential in preventing tumors

A new study has confirmed that research done with zebrafish may be able to play a critical role in learning about the genetic basis of cancer and the mutations that can lead to it - and identified one gene in particular, B-myb, whose function is essential to preventing tumors.

The findings were published in a professional journal, Proceedings of the National Academy of Sciences, by researchers from Oregon State University and two Boston hospitals, the Brigham and Women's Hospital and Children's Hospital.

The research also indicates that zebrafish may be a key to faster, less expensive studies on cancer and carcinogens, as well as a tool to lower the cost for drug development, OSU experts said.

The first comprehensive cancer research studies using this small, striped tropical fish were begun at OSU over 10 years ago, and the species has become an important tool in medical research programs around the world.

"It's increasingly clear that in zebrafish we have an animal model that is inexpensive, easy to work with and extremely useful for study of human cancers," said Jan Spitsbergen, a fish pathologist in OSU's Center for Fish Disease Research. "We've now proven that most of the carcinogens that affect humans are also active in zebrafish and can lead to the same types of cancer, whether it's in the brain, blood, reproductive organs or elsewhere."

The newest finding about the gene B-myb is especially compelling, said Spitsbergen. The B-myb gene has been conserved through hundreds of millions of years of divergent evolution in species ranging from worms to fruit flies, fish and humans.

When it functions normally, B-myb appropriately regulates cell proliferation. When it becomes mutated, either through genetic predisposition or environmental influences, the formation of tumors can dramatically increase, scientists say. The gene appears to be particularly relevant to human leukemias.

OSU's fish disease research programs date back several decades, and the university first developed the rainbow trout as a useful model for cancer research. Those studies, among others, helped to determine that aflatoxin contaminants which can be found in some foods are a powerful carcinogen - and are still a major cause of liver cancer in some developing nations.

Zebrafish, however, are a fascinating species because the fish embryos are literally transparent and can be directly observed at early developmental stages better than almost any other animal species. They had been used for years in studying everything from the immune system to cardiovascular disease and skeletal development.

In the mid-1990s, OSU researchers began the use of zebrafish in cancer research.

OSU scientists conducted studies on a wide variety of carcinogens and a complete histologic examination of all major organs, the first work of that type. In recent years collaboration has also been extensive with colleagues at the University of Oregon, where the federally funded Zebrafish International Resource Center archives, propagates and distributes the many mutant lines of zebrafish now developed worldwide to aid research on specific genes in development and disease.

This research has proven that the mechanism of cancer prevention in fish is remarkably similar to that of humans, including the genes involved.

"Zebrafish are now changing the face of cancer research," Spitsbergen said. "They can be managed in a laboratory almost anywhere, they reproduce quickly, lend themselves well to genetic manipulation, can efficiently test high numbers of possible drug therapies, and might tell you in three months what it would take two years to find out with other animal models."

"This low cost, efficient research should speed up drug development, save many millions of dollars and help lead to new cancer therapies." Using zebrafish, OSU has extensively studied two groups of carcinogens, polyaromatic hydrocarbons, or PAHs, and nitrosamines. Both of these groups can be produced by normal living activities, ranging from preserved foods to smoking and use of wood stoves. University researchers have also been active in studies on dioxin and PCBs, both concerns in the process of carcinogenesis.

"With zebrafish as a model we should be able to better determine what types and levels of environmental carcinogens are a real health concern," Spitsbergen said. "And we should also be able to rapidly test and develop new approaches to treat cancer."