"Obesity Gene" Causes Cancer Of Fat Tissue, Schepens Scientists Find

The gene, known as HMG I-C, causes tumors called lipomas, a common tumor in fat tissue in humans. Lipomas start as benign growths, but can become malignant liposarcomas as they grow. Lipomas are the most common form of mesenchymal tumors found in humans.

"There is now strong evidence that targeting this molecule may be useful both for the treatment of obesity in humans and the treatment of lipomas. It is likely that therapeutic agents which block the expression of the HMG I-C would be effective in the treatment of these two major clinical problems ," said Santa J. Ono, Ph.D., Associate Scientist at The Schepens Eye Research Institute and Associate Professor at Harvard Medical School.

Ono and his colleagues report their findings in The Journal of Biological Chemistry, scheduled for publication on May 12, 2000. The paper has been online at the journal's web site (www.jbc.org) since March 15. Coauthors are Paola Arlotta, Ph.D., and Albert K.-F. Tai, both of The Schepens Eye Research Institute; Guidalberto Manfioletti, Ph.D., University of Trieste, Italy; Charles Clifford, Ph.D., Charles Rivers Laboratories, Wilmington, Mass.; and Gilbert Jay, Ph.D., OriGene Technologies, Rockville, Md.

Previous epidemiologic data had shown that the HMG I-C gene is defective in many mesenchymal tumors. The Ono team has proven a direct role for the HMG I-C gene in lipoma formation by creating transgenic mouse lines that overexpress the defective HMG I-C gene in all cells of the body. The transgenic mice are obese early in life and develop tumors of the adipose (fat) tissue in adult life. About 25 percent of the transgenic mice develop tumors, while control mice, or normal mice, showed no evidence of tumor formation.

The researchers also found that no tumors formed in other tissues of the body, just in fat tissue. However, other researchers in Ono's group have found that the HMG I-C gene also may contribute to human retinoblastomas, a tumor of the eye. "This is really a new type of oncogene, a structural chromosomal protein contributing to tumor formation," Ono said.

Previous research done at the University of Medicine and Dentistry of New Jersey has shown that the HMG I-C gene appears to help mice store fat. Transgenic mice lacking the gene can eat voraciously without getting fat. The Ono team has performed complementary experiments by overexpressing the gene, and noted both obesity and tumor growth.

Ono's research was funded by grants from the National Institutes of Health, the Lucille P. Markey Foundation, the Howard Hughes Medical Institute and the Research to Prevent Blindness Foundation, America.

The Schepens Eye Research Institute, an affiliate of Harvard Medical School, is the largest independent eye research center in the nation, both in size of faculty and support from the National Eye Institute. It has a renowned faculty of more than 60 scientists, including immunologists, molecular and cell biologists and physicists who investigate cures for blinding eye diseases and aids for victims of low vision. Many diagnostic techniques and devices, surgical methods and medications related to eye diseases were developed by Institute faculty.