Role of Tumor Suppressor Genes in a Multistep Model of Carcinogenesis

  • Jeff A. Boyd
  • J. Carl Barrett
Part of the Basic Life Sciences book series (BLSC, volume 57)


Most cancers are clonal in origin, arising from a single aberrant cell1. The multistep nature of this process is now a widely accepted paradigm2, and is supported by several lines of evidence from both clinical oncology and experimental models. Among these are: 1) histopathological observations of human tumors reveal multiple stages of tumor progression such as dysplasia and carcinoma in situ3; 2) mathematical models based on age-specific tumor incidence curves are consistent with four to seven independent hits required for tumor formation4; 3) studies of genetic predisposition to cancer in some families suggest that one step in the carcinogenic process is a germline mutation and that additional somatic events are required for full neoplastic development5; 4) well documented experimental systems, including the two-stage model of chemical carcinogenesis in rodent skin6,7 and liver8, show that different chemicals affect qualitatively different stages in the carcinogenic process; 5) cell culture studies reveal that chemical carcinogen-induced neoplastic transformation of normal cells involves a progressive process9; 6) cell culture studies with viral and tumor-derived oncogenes show that the neoplastic conversion of normal cells generally requires multiple cooperating oncogenes10; and 7) studies on the development of tumors in transgenic mice carrying activated proto-oncogenes in their germline indicate that the tumors which arise are clonal in origin, suggesting that additional somatic events besides activation of two cooperating oncogenes are required for full malignant development11.


Tumor Suppressor Gene Cell Hybrid Actin Microfilament Restriction Fragment Length Polymorph Retinoblastoma Tumor 
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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Jeff A. Boyd
    • 1
  • J. Carl Barrett
    • 1
  1. 1.Laboratory of Molecular CarcinogenesisNational Institute of Environmental Health SciencesResearch Triangle ParkUSA

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