Genetic and Epigenetic Regulation of the Metastatic Phenotype: A Basis for Resolving the Controversy Regarding its Selective or Random Nature and Variable Phenotypic Stability

  • R. S. Kerbel
  • P. Frost
  • R. G. Liteplo
Part of the Developments in Oncology book series (DION, volume 41)

Summary

Considerable controversy exists as to whether the metastatic phenotype is selective or random in nature, and if selective, whether it is always inherited and expressed in a stable, or unstable, manner. Which of the alternatives is correct has important implications and ramifications for virtually every aspect of the experimental study of metastasis. Based on analogous experimental situations (e.g., drug resistance due to gene amplification) and results from two separate experimental systems obtained in our laboratories, we conclude that the metastatic phenotype is indeed selective in nature, i.e., there are genotypically distinct subpopulations of metastatic variants. However, the ways in which the genetic information relevant to the metastatic phenotype is regulated and expressed will determine the relative stability of the phenotype: both unstable and stable variants can co-exist. We hypothesize that changes in DNA methylation (i.e., of 5-methylcytosine) is one of several possible mechanisms which can account for an unstably expressed phenotype. We also argue that the selection pressure required to isolate the stable variety of variant may be much stronger than what many investigators have previously used and can account for some of the discrepancies in the experimental metastasis literature.

Keywords

Corticosteroid Methotrexate Prolactin Thymidine Cytosine 

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Copyright information

© Martinus Nijhoff Publishing, Boston 1986

Authors and Affiliations

  • R. S. Kerbel
    • 1
    • 2
  • P. Frost
    • 1
    • 2
  • R. G. Liteplo
    • 1
    • 2
  1. 1.Department of PathologyQueen’s UniversityKingstonCanada
  2. 2.Department of Cell BiologyUniversity of Texas System Cancer Center, M.D. Anderson Hospital and Tumor InstituteHoustonUSA

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