Blocking of tumor promoter-induced AP-1 activity inhibits induced transformation in JB6 mouse epidermal cells.
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- Z Dong
- Biological Carcinogenesis and Development Program, PRI/DynCorp, Frederick, MD.
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- M J Birrer
- Biological Carcinogenesis and Development Program, PRI/DynCorp, Frederick, MD.
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- R G Watts
- Biological Carcinogenesis and Development Program, PRI/DynCorp, Frederick, MD.
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- L M Matrisian
- Biological Carcinogenesis and Development Program, PRI/DynCorp, Frederick, MD.
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- N H Colburn
- Biological Carcinogenesis and Development Program, PRI/DynCorp, Frederick, MD.
説明
<jats:p>AP-1 transcriptional activity is stimulated by the transformation promoters phorbol 12-myristate 13-acetate ("12-O-tetradecanoylphorbol 13-acetate," TPA) and epidermal growth factor (EGF) in promotion-sensitive (P+) but not in promotion-resistant (P-) JB6 mouse epidermal cell lines. Although TPA stimulates expression of the jun and fos family genes, only c-jun expression shows higher elevation in P+ cells than in P- cells. The present study tests the hypothesis that induced AP-1 activity is required for tumor promoter-induced transformation in JB6 P+ cells. Both retinoic acid and the glucocorticoid fluocinolone acetonide inhibited basal and TPA-induced AP-1 activities that were tested with a stromelysin promoter-chloramphenicol acetyltransferase reporter gene in P+ cells. Since both retinoic acid and fluocinolone acetonide are active in inhibiting TPA-induced anchorage-independent transformation of P+ cells in the dose range that blocks TPA-induced AP-1 activity, their antipromoting effects may occur through inhibition of AP-1 activity. To test the hypothesis with a more specific inhibitor, stable clonal transfectants of P+ cells expressing dominant negative c-jun mutant encoding a transcriptionally inactive product were analyzed. All transfectants showed a block in TPA and EGF induction of AP-1 activity. All transfectants also showed inhibition of TPA-induced transformation, and most transfectants showed a block in EGF-induced transformation. These results indicate that AP-1 activity is required for TPA- or EGF-induced transformation. This work demonstrates that a specific block in induced AP-1 activity inhibits tumor promoter-induced transformation.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 91 (2), 609-613, 1994-01-18
Proceedings of the National Academy of Sciences
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詳細情報 詳細情報について
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- CRID
- 1363388845114582016
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- NII論文ID
- 30016297444
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- ISSN
- 10916490
- 00278424
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- データソース種別
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