Mar. 4, 1998 Philadelphia, PA, March 1, 1998 -- Scientists at The Wistar Institute, working in collaboration with researchers from around the world, have identified a new gene, called BAP1, associated with breast and lung cancer development. The group's findings, which may have major implications for the treatment of breast and lung cancers, appear in today's issue of Oncogene.
BAP1, discovered in the Wistar laboratory of Dr. Frank J. Rauscher III, encodes an enzyme that helps to regulate levels of BRCA1, a gene known to cause hereditary breast and ovarian cancers.
Three years ago, scientists in Utah identified the BRCA1 gene, which was a landmark accomplishment in cancer research. The discovery of BRCA1 made it possible to genetically test for carriers of the gene. When a faulty BRCA1 gene is inherited, a woman's chances of developing breast and/or ovarian cancer are greater than 80 percent during her lifetime.
Since BRCA1's discovery, scientists around the world have been working feverishly to discover the functions of the BRCA1 protein. Proteins, the main ingredients in cells, have shapes and functions that are genetically defined.
With a clear understanding of the role BRCA1 plays in normal breast development, scientists can better explain how mutations of the BRCA1 gene might alter that process. Laboratory studies have revealed that BRCA1 and BAP1 form a complex in the cell that controls BRCA1's activities, including its deterioration.
The Wistar investigators have also learned that, like BRCA1, the BAP1 gene is a cancer gene. Mutations of BAP1 have been found in non-small-cell lung cancers.
BAP1 and BRCA1 are both tumor suppressor gene products that appear to be part of a large complex that controls the growth of breast and lung epithelial cells. Mutations in either BAP1 or BRCA1 abolish this complex and lead to the development of cancer.
The discovery of BAP1 makes it possible to do genetic testing for its presence, making it a potential target for drugs that combat breast and lung cancers.
The team of Wistar scientists who conducted the research on BAP1 includes Drs. Frank J. Rauscher III, David E. Jensen, Alexander M. Ishov, David C. Schultz, Gerd G. Maul, Nickolai Barlev, Shelley L. Berger and George C. Prendergast. Collaborating scientists are from the Hamon Center for Therapeutic Oncology Research at the University of Texas Southwestern Medical Center; the John F. Kennedy Institute and The Department of Medical Genetics at The Panum Institute, Copenhagen, Denmark; the Department of Molecular Genetics, Novo Nordisk, Bagsvaerd, Denmark; the Department of Biochemistry, Emory University, Atlanta, Georgia; the Department of Molecular and Cellular Engineering, University of Pennsylvania School of Medicine.
Funding for this Wistar research has been provided, in part, by the Susan G. Koman Breast Cancer Foundation. Other support has come from the National Institutes of Health, Pew Scholars Program in the Biomedical Sciences, Irving A. Hansen Memorial Foundation, Mary A. Rumsey Memorial Foundation, Danish Cancer Society, Charles E. Culpepper Foundation, American Cancer Society and National Cancer Institute.
The Wistar Institute, established in 1892, was the first independent medical research facility in the country. For more than 100 years, Wistar scientists have been making history and improving world health through their development of vaccines for diseases that include rabies, German measles, infantile gastroenteritis (rotavirus), and cytomegalovirus; discovery of molecules like interleukin-12, which are helping the immune system fight bacteria, parasites, viruses and cancer; and location of genes that contribute to the development of diseases like breast, lung and prostate cancer. Wistar is a National Cancer Institute Cancer Center.
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