Thomas M. Birkenmeier, M.D.

DEPARTMENT OF Internal Medicine
Keywords: cancer, amplified DNA, n-myc oncogene, extracellular matrix

Many tumors contain amplified DNA sequences encoding oncogenes. For example, small cell lung cancer and neuroblastoma often contain amplified DNA encoding the N-myc oncogene. We have been investigating the effects of various agents on the tumorigenicity of these cancers and have discovered that bromodeoxyuridine converts a highly malignant small cell lung cancer line to a nonmalignant one when assayed by tumor growth in nude mice. Concurrent with this change in phenotype is a loss of the amplified N-myc gene and a dramatic upregulation of the expression of a variety of extracellular matrix proteins and their cell surface receptors. We plan to extend these studies to other tumors and other chemotherapeutic agents with the hope of being able to use these clinically to treat refractory tumors. Additionally, we have demonstrated that N-myc inhibits the expression of extracellular matrix proteins and their cell surface receptors, and we are investigating the molecular mechanisms controlling this response.