N-myc can cooperate with ras to transform normal cells in culture.
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.
D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004273:DNA, Neoplasm / Q000032:analysis; D004622:Embryo, Mammalian; D005822:Genetic Vectors; D009857:Oncogenes; D012334:RNA, Neoplasm / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D014162:Transfection
D004273:DNA, Neoplasm; D012334:RNA, Neoplasm