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UVA studies potential target for skin cancer treatment

October 04, 2006

When normal skin cells become a melanoma tumor, they sometimes turn on genes not usually found in the skin. According to researchers at the University of Virginia Health System, some of these genes are normally active in the male testis at the time sperm are formed.

The genes, called cancer-testis antigens, could be useful targets for drugs that could selectively kill a melanoma tumor, while sparing the rest of the body's tissues. The antigens could also help researchers develop a vaccine to stimulate the immune system to attack and suppress melanoma tumors.

"Scientists are beginning to see patterns in the profile of genes expressed in individual tumor cells," said John C. Herr, Ph.D., professor of cell biology at UVa and a scientist at the UVa Cancer Center. " Patients who express a given cancer-testis antigen may eventually be helped by such selective therapies. This scenario represents one aspect of the growing opportunities envisioned for personalized medicine."

Scientists at the UVa Cancer Center have studied melanoma tumors from patients at various stages of the disease over the last few years. They discovered that more than half of these tumors made the cancer-testis antigens, called SPANX proteins. In a study published in the Sept. 29, 2006 online edition of the Journal Molecular Human Reproduction, Herr and his UVa research team showed that the SPANX proteins play a role in the formation of the nuclear envelope of the developing human spermatid. The paper can be found online at this link: http://molehr.oxfordjournals.org/cgi/content/abstract/gal079.

"The SPANX proteins appear at the last stages of sperm production, " explained Anne Westbrook, Ph.D., lead author of the study and a researcher in UVa's department of biochemistry and molecular genetics. "Interestingly, the SPANX proteins remain restricted to regions of the nuclear envelope that do not touch the acrosome, an organelle involved in fertilization."

Researchers at the University of Virginia Health System first identified and named the SPANX gene family in 2000. "UVa continues to make strides in understanding select areas of the human genome," Herr said. "Although the X chromosome on which these genes lie is often associated with determination of female gender, in this case the X chromosome contains genes involved in formation of the sperm. This gene family is now attracting considerable interest from other groups."

For example, scientists at the National Cancer Institute recently discovered that the SPANX family represents one of the most rapidly evolving regions of the human genome. The five SPANX genes appear to have evolved by gene duplication from a single common ancestor since the rise of hominoids. African great apes like chimpanzees, bonobos, gorillas, and orangutans have SPANX, but monkeys do not.

"SPANX represents a rapidly evolving gene family located on the X chromosome involved in the development of the spermatid nucleus," Herr said.

"While our recent findings represent an important step in our knowledge, the overall role of SPANX proteins in reproduction and the precise molecular pathways in which they function in the testis remain to be explored."

One of the intriguing features about the SPANX proteins is that two gene locations, for familial forms of prostate and testicular cancer, map to the SPANX region on the X chromosome. "These findings underscore the need to better understand the function of this rapidly evolving gene family" Herr said.

University of Virginia Health System