Human annexin 1 is highly expressed during the differentiation of the epithelial cell line A 549: involvement of nuclear factor interleukin 6 in phorbol ester induction of annexin 1.
The role of annexin 1 (Ax 1) in cell differentiation was studied in the A 549 epithelial cell line, a human lung adenocarcinoma line, that responds to phorbol esters and glucocorticoids by induction of differentiated properties. Ax 1 has also been reported to be involved in the control of cell proliferation. We report that Ax 1 synthesis occurs upon phorbol 12-myristate 13-acetate (PMA) treatment of A 549 cells and its appearance is correlated with the presence of dipeptidyl peptidase IV, or CD26, a marker of epithelial cell differentiation. In addition, using transfection experiments and site-directed mutagenesis with the Ax 1 promoter coupled to a reporter gene, we report that a unique region of the Ax 1 promoter confers the response of the reporter gene to PMA and dexamethasone. This response to PMA and/or dexamethasone involves the induction of the synthesis and/or the activity of trans/cis-activating transcriptional factors. Furthermore, we have delineated the mechanism of the transcriptional activation of Ax 1 by PMA and the involvement of a specific transcription factor, nuclear factor interleukin 6 (C/EBP beta).
Solito
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Institut Cochin de Génétique Moléculaire, Institut National de la Santé et de la Recherche Médicale Unité 332, Paris, France. solito@icgm.cochin.inserm.fr
de Coupade
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Parente
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Flower
R J
RJ
Russo-Marie
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D000230:Adenocarcinoma; D017305:Annexin A1 / Q000235:genetics*; D022762:CCAAT-Enhancer-Binding Proteins; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D018819:Dipeptidyl Peptidase 4 / Q000032:analysis; D004847:Epithelial Cells / Q000502:physiology*; D005938:Glucocorticoids / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms; D015735:Mifepristone / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011993:Recombinant Fusion Proteins; D017384:Sequence Deletion; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects*; D014162:Transfection; D014407:Tumor Cells, Cultured
D017305:Annexin A1; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D006727:Hormone Antagonists; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D015735:Mifepristone; D003907:Dexamethasone; D018819:Dipeptidyl Peptidase 4; D013755:Tetradecanoylphorbol Acetate