Multistage carcinogenesis induced by ras and myc oncogenes in a reconstituted organ

Cell. 1989 Mar 24;56(6):917-30. doi: 10.1016/0092-8674(89)90625-9.


ras and myc oncogenes were able to induce distinct phenotypic alterations, resembling different types of premalignant lesions, when introduced into approximately 0.1% of the cells used to reconstitute the mouse prostate gland. While ras induced dysplasia in combination with angiogenesis, myc induced a hyperplasia of the otherwise normally developed organ. ras and myc together induced primarily carcinomas. However, tumor progression was also associated with additional genetic alterations involving gene amplification. Our data indicate that specific types of benign premalignant lesions may reflect the activation of different single oncogenes, and that the consecutive activation of multiple oncogenes could be a causal event in the step-like progression of tumorigenesis.

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / chemically induced*
  • Cell Transformation, Neoplastic / pathology
  • Gene Expression Regulation
  • Hyperplasia
  • Male
  • Mice
  • Mice, Inbred Strains
  • Neoplasm Staging
  • Oncogenes
  • Phenotype
  • Prostate / pathology
  • Prostatic Neoplasms / chemically induced
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / pharmacology*
  • Proto-Oncogene Proteins c-myc
  • Proto-Oncogene Proteins p21(ras)
  • Retroviridae / genetics
  • Retroviridae Infections / pathology


  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myc
  • Proto-Oncogene Proteins p21(ras)