In human neuroblastoma, amplification of the N-myc oncogene is closely correlated with increased metastatic ability. The mechanism by which over- expression of the N-myc oncogene contributes to the increased metastatic ability of neuroblastoma tumor cells is largely unknown. The objective of this study is to elucidate the changes in cellular gene expression that occur in neuroblastoma tumor cells in which the N-myc gene is over- expressed and to investigate whether these changes contribute to the increased metastatic ability of the N-myc-amplified neuroblastomas. We will also investigate how the N-myc oncogene acts to cause these changes in cellular gene expression. To date, we have identified several genes whose expression is dramatically reduced by the N-myc oncoprotein in neuroblastoma: they encode the MHC class I antigens, the gene encoding neural cell adhesion molecule (NCAM), and three different isoforms of protein kinase C. We plan a detailed examination of the mechanism by which the N-myc protein acts to suppress the expression of MHC class I antigens and NCAM polypeptides in neuroblastoma tumor cells. Furthermore, we will investigate whether the reduced expression of these genes is required for the manifestation of the metastic phenotype of neuroblastoma. Demonstrating the mechanism by which the N-myc oncogene deregulates cellular gene expression is instrumental in understanding how myc oncogenes contribute to malignant transformation. Furthermore, our studies should help to elucidate the mechanism by which the N-myc oncogene contributes to the increased metastatic ability of neuroblastoma tumor cells. Elucidating the process of tumor progression in neuroblastoma may eventually lead to therapies that specifically interfere with the process of tumor metastasis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA052756-03
Application #
3197599
Study Section
Pathology A Study Section (PTHA)
Project Start
1991-04-01
Project End
1995-03-31
Budget Start
1993-04-15
Budget End
1994-03-31
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199