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In vitro analysis of multistage carcinogenesis
P Nettesheim1, D J Fitzgerald, H Kitamura
1Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Environmental Health Perspectives
|November 1, 1987
Summary
Neoplastic transformation of rat tracheal epithelium (RTE) begins with disrupted stem cell replication control. Later stages involve loss of growth restraint and activation of growth-promoting genes, leading to cancer.
Area of Science:
- Cell Biology
- Cancer Research
- Toxicology
Background:
- Neoplastic transformation is a multistep process.
- Rat tracheal epithelium (RTE) is a model for studying carcinogenesis.
- Carcinogen exposure can initiate cellular changes.
Purpose of the Study:
- To describe key events in the neoplastic transformation of RTE.
- To identify early and late events in RTE cell transformation.
- To understand the role of stem cell regulation in cancer development.
Main Methods:
- In vivo and in vitro exposure of RTE to carcinogens.
- Detection of initiated stem cells under selective culture conditions.
- Analysis of stem cell proliferation, self-renewal, and differentiation.
Main Results:
- Initiated stem cells show altered responses to proliferation controls.
- Disrupted stem cell replication control is an early event.
- Progression involves loss of retinoic acid responsiveness (immortal growth variants) and inappropriate growth factor receptor expression (neoplastic growth variants).
Conclusions:
- Loss of growth-restraining mechanisms is an early event in RTE transformation.
- Activation of growth-stimulatory mechanisms is a late event.
- Understanding these stages is crucial for cancer prevention and treatment strategies.