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Granulocyte-macrophage colony stimulating factor gene expression and function during tumor promotion
F M Robertson1, G N Bijur, A S Oberyszyn
1Department of Medical Microbiology and Immunology, College of Medicine, Ohio State University, Columbus 43210.
Carcinogenesis
|May 1, 1994
Summary
Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a key role in skin tumor promotion by stimulating keratinocyte proliferation and leukocyte infiltration. Inhibiting GM-CSF reduces inflammatory responses during tumor promotion.
Area of Science:
- Immunology
- Dermatology
- Oncology
Background:
- Granulocyte-macrophage colony-stimulating factor (GM-CSF) is implicated in cutaneous inflammation.
- Limited data exists on GM-CSF's temporal gene expression and function during skin tumor promotion.
Purpose of the Study:
- To investigate the role and temporal gene expression of GM-CSF in skin tumor promotion in SENCAR mice.
- To identify target cells and functions of GM-CSF in this process.
Main Methods:
- Competitive reverse transcriptase polymerase chain reaction (RT-PCR) for gene expression analysis.
- Immunochemical and autoradiographic studies for protein localization.
- In vivo experiments using recombinant GM-CSF and anti-GM-CSF antibodies.
Main Results:
- Topical 12-O-tetradecanoylphorbol-13-acetate (TPA) induced dose- and time-dependent GM-CSF gene expression, peaking at 3 hours.
- GM-CSF protein was found in keratinocytes and leukocytes.
- Recombinant GM-CSF enhanced keratinocyte proliferation and leukocyte infiltration; anti-GM-CSF antibodies inhibited inflammation.
Conclusions:
- GM-CSF is actively transcribed during tumor promotion and targets epidermal keratinocytes and leukocytes.
- GM-CSF acts as a signaling peptide, promoting epidermal proliferation, priming neutrophils, and regulating leukocyte migration.