Related Experiment Videos
N-myc can cooperate with ras to transform normal cells in culture
Abstract:
N-myc, a cellular gene bearing homology to the c-myc protooncogene, is frequently amplified and overexpressed in a highly restricted set of related tumors, most notably neuroblastomas and retinoblastomas. We have examined the possibility that N-myc may play a causal role in the genesis of these tumors by defining its ability to transform primary cells in tissue culture. Using an N-myc expression construct capable of producing constitutively deregulated levels of full-length murine N-myc mRNA, we demonstrate that a deregulated N-myc gene can cooperate with the activated Ha-ras oncogene to cause tumorigenic conversion of normal embryonic fibroblasts in a manner indistinguishable from the deregulated c-myc oncogene. Cell lines established from N-myc/ras-transformed foci express high levels of the N-myc gene, and such lines are similar to c-myc/ras transformants in their ability to grow in soft agar and cause tumors in syngeneic rats. These results illustrate that N-myc does encode a c-myc-like transforming activity and that this transforming activity is not specific for the very restricted set of tumors in which N-myc is normally amplified or overexpressed.
Insights
The N-myc gene, similar to c-myc, can transform normal cells when deregulated. This oncogenic activity is not limited to the specific tumors where N-myc is typically overexpressed.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- N-myc is a protooncogene homologous to c-myc.
- N-myc amplification and overexpression are observed in neuroblastomas and retinoblastomas.
Purpose of the Study:
- To investigate the potential causal role of N-myc in tumor genesis.
- To determine if N-myc possesses transforming activity in primary cells.
Main Methods:
- Utilized an N-myc expression construct for deregulated mRNA production.
- Co-expressed N-myc with the activated Ha-ras oncogene in embryonic fibroblasts.
- Assessed tumorigenic conversion and characterized transformed cell lines.
Main Results:
- Deregulated N-myc cooperated with Ha-ras to transform fibroblasts, similar to c-myc.
- Transformed cell lines showed high N-myc expression and oncogenic properties (soft agar growth, tumor formation).
- N-myc demonstrated a c-myc-like transforming activity.
Conclusions:
- N-myc encodes a transforming activity akin to c-myc.
- This N-myc transforming activity is not restricted to the specific tumor types where it is usually amplified or overexpressed.