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Phorbol ester inhibits surfactant protein SP-A and SP-B expression
G S Pryhuber1, M A O'Reilly, J C Clark
1Division of Pulmonary Biology, Children's Hospital Medical Center, University of Cincinnati College of Medicine, Ohio 45267-0541.
The Journal of Biological Chemistry
|December 5, 1990
Summary
The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) reduces pulmonary surfactant proteins SP-A and SP-B expression and synthesis in lung cancer cells. This suggests protein kinase C modulates surfactant protein gene expression.
Area of Science:
- Pulmonary medicine
- Cell biology
- Biochemistry
Background:
- Pulmonary surfactant proteins SP-A and SP-B are crucial for lung function.
- Tumor promoters can influence cellular processes, including protein expression.
Purpose of the Study:
- To investigate the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) on SP-A and SP-B expression in a human lung adenocarcinoma cell line.
- To elucidate the mechanism by which TPA affects surfactant protein synthesis.
Main Methods:
- Human pulmonary adenocarcinoma H441-4 cells were treated with TPA.
- Cellular SP-A and SP-B content and mRNA levels were measured.
- [35S]methionine incorporation assessed de novo protein synthesis.
- Binding studies with [3H]PDBu and actinomycin D were used to explore mechanisms.
Main Results:
- TPA significantly decreased cellular SP-A content and de novo synthesis in a time- and dose-dependent manner.
- SP-A and SP-B mRNA levels were reduced by TPA, with decreases occurring more rapidly than with actinomycin D.
- Inhibition of SP-A by phorbol 12,13-dibutyrate (PDBu) correlated with PDBu binding, suggesting a role for protein kinase C.
Conclusions:
- TPA inhibits the expression and synthesis of pulmonary surfactant proteins SP-A and SP-B in lung adenocarcinoma cells.
- The inhibitory effects of TPA on surfactant protein mRNA require continued gene transcription.
- Protein kinase C likely plays a role in modulating surfactant protein expression in these cells.