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Lab study: restored gene thwarts advanced tumors in mice (5-20-99)

Researchers from The University of Texas Health Science Center at San Antonio are reporting the successful suppression of pituitary, thyroid and adrenal tumors in mice.

Furthermore, the scientists found that replacement of a defective gene called the retinoblastoma susceptibility gene (RB) slowed or prevented development of lung metastasis originating from tumors of the thyroid gland. Metastasis occurs when cancer cells spread from a primary site to another part of the body. This type of cancer frequently is difficult to treat.

In laboratory experiments, one group of mice received RB therapy while another control group did not. The active treatment group received intravenous injections for three weeks with liposomes (fatlike envelopes) containing the RB gene. At the end of the experiment, 84 percent of the control mice had metastatic cells in their lungs. In the treated group, only 12 percent of mice had such cells in their lungs.

The Health Science Center researchers, collaborating with peers at the University of Pittsburgh, published these findings in a spring issue of the Proceedings of the National Academy of Sciences. The San Antonio authors are appointed in the Health Science Center's Department of Molecular Medicine and are housed at the center's U. T. Institute of Biotechnology in the Texas Research Park west of San Antonio.

The scientists studied mice with only a single copy of the RB gene. Most of the animals developed multiple neuroendocrine neoplasia, a cancerous condition in cells of the pituitary, adrenal, thyroid and parathyroid glands. All tumors lacked the RB gene. By the time the mice were 350 days old, tumors had formed from the cells of the neuroendocrine glands. At this point, the treatment group of mice began receiving RB therapy.

"Loss of RB function is essential for initiation of tumor growth in multiple types of neuroendocrine cells in these mice," said Alexander Nikitin, M.D., Ph.D., instructor in the Department of Molecular Medicine. žIn the study just published, we demonstrate that RB deficiency remains important during subsequent tumor formation and even during the most advanced stage of tumor progression. Because of these observations, we have the hope that placing RB back into human RB-deficient metastatic tumors, such as small-cell lung cancer, may be effective therapy for these cancers."

Dr. Nikitin is listed as first author on the paper. Co-authors are María Juárez-Pérez, M.D., a Health Science Center fellow; Wen-Hwa Lee, Ph.D., professor and chair of the Department of Molecular Medicine and director of the Institute of Biotechnology; and Drs. Song Li and Leaf Huang of the Department of Pharmacology at the University of Pittsburgh School of Medicine.

Contact: Will Sansom