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Twin genes on chromosome 3 have ability to put kibosh on some cancers, experiments show

Two genes that, when healthy, put the brakes on lung, ovarian and possibly prostate cancer continue to be exciting avenues of study at The University of Texas Health Science Center at San Antonio (UTHSCSA).

"Semaphorin 3B is a gene with a lot of promise for stopping many cancers," said Susan L. Naylor, Ph.D., professor of cellular and structural biology at UTHSCSA and lead author of papers in Cancer Research and Genomics, including two articles this year. "We have conclusive data for its role in suppressing lung and ovarian cancer, and we have some new data on prostate cancer, that there may be some involvement there, as well." Dr. Naylor's laboratory team and a competing team at another institution published the first papers on the function of SEMA3B.

3B is located on the short arm of human chromosome 3 in a region known to be mutated in lung cancer. The research team inserted 3B into cancer cells that lacked a working copy of the gene. "After the implant, the aberrant cells no longer made tumors," Dr. Naylor said.

Next to it on chromosome 3 is a closely related gene, semaphorin 3F, which plays a role in a slightly different spectrum of cancers. Dr. Naylor's lab was the first to discover SEMA3F and her group is the only one to publish on its function. 3F is one of only 30 to 50 tumor-suppressor genes known to scientists.

In addition to suppressing cancer, the semaphorin genes appear to be involved in development of neurons (nerve cells) and blood vessels (a process called angiogenesis). "It's too soon to understand how this works, but this family of genes seems to have a hand in a variety of signaling processes," Dr. Naylor said.

The UTHSCSA team is investigating variants of the genes to determine which are most closely connected with cancer susceptibility. Jacob Kagan, Ph.D., now at the National Cancer Institute, worked with Dr. Naylor as a visiting scientist in her laboratory. "Dr. Naylor is an outstanding scientist who pioneered the discovery and cloning of the SEMA3F gene," he said. "Her laboratory has shown that insertion of a healthy copy of the gene into a tumor that lacks the normal active form of the gene can suppress tumor development and progression."

"Dr. Naylor's work on these tumor-suppressor genes holds great promise to advance our understanding of the biology of lung, ovarian and prostate cancer," said Brian A. Herman, Ph.D., professor and chairman of cellular and structural biology at UTHSCSA. "These are prevalent cancers that can be difficult to treat, and her ability to inhibit their formation using both genes is a major step on the path to preventing and treating these cancers."

Contact: Will Sansom