Document Detail

Retinoids and phorbol esters alter release of fibronectin from enucleated cells.
MedLine Citation:
PMID:  6959135     Owner:  NLM     Status:  MEDLINE    
Addition of 12-tetradecanoylphorbol 13-acetate (TPA) to cultures of intact Swiss mouse 3T3 fibroblasts induced a dose-dependent increase in ornithine decarboxylase (OrnDCase) activity. Over the same concentration range, 10(-9) to 10(-6) M, TPA induced the release of radioactively labeled fibronectin (FN) from the cells into the culture medium. Retinoic acid, a derivative of vitamin A, inhibited in a dose-dependent manner both the increase in OrnDCase activity and the release of FN induced by TPA. To examine the effects of TPA and retinoic acid in enucleated cells, the cells were treated with 7.5 micrograms of cytochalasin B per ml of medium during centrifugation at 10,000 X g for 35 min at 37 degrees C. In a series of five experiments, the treated cells were 94.7 +/- 4.8% (+/- SEM) enucleated as measured by [3H]thymidine incorporation and verified by Giesma staining for nuclei. In the enucleated cells, TPA did not induce increased OrnDCase activity but did induce FN release in a dose-dependent fashion over the same concentration range effective for FN release from intact cells. Moreover, addition of retinoic acid to the enucleated cells inhibited the phorbol ester-induced release of FN in a dose-dependent manner. A series of phorbol ester derivatives showed the same order of activity in causing FN release from the enucleated cells as reported for inducing OrnDcase activity in intact cells or in promoting mouse skin tumors in vivo. Similarly, several retinoids were tested for their ability to inhibit the phorbol ester-induced release of FN from enucleated cells. The efficacy of the retinoids in preventing FN release paralleled their activity in inhibiting phorbol ester-induced OrnDCase activity and skin tumor promotion, as reported in the literature. We conclude that at least one aspect of tumor promotion induced by phorbol esters--the loss of FN--does not require the cell nucleus, and further, that retinoids can inhibit this aspect of tumor promotion without nuclear involvement.
S D Bolmer; G Wolf
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  79     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1982 Nov 
Date Detail:
Created Date:  1983-01-27     Completed Date:  1983-01-27     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  6541-5     Citation Subset:  IM    
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MeSH Terms
Cell Membrane / physiology*
Cell Nucleus / physiology*
Cells, Cultured
Enzyme Induction / drug effects
Fibronectins / metabolism*
Ornithine Decarboxylase / biosynthesis
Phorbols / pharmacology*
Structure-Activity Relationship
Tetradecanoylphorbol Acetate / pharmacology*
Tretinoin / pharmacology*
Grant Support
Reg. No./Substance:
0/Fibronectins; 0/Phorbols; 16561-29-8/Tetradecanoylphorbol Acetate; 302-79-4/Tretinoin; EC Decarboxylase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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