HUMAN ANNEXIN-1 IS HIGHLY EXPRESSED DURING THE DIFFERENTIATION OF THEEPITHELIAL-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 th e A 549 epithelial cell line, a human lung adenocarcinoma line, that r esponds to phorbol esters and glucocorticoids by induction of differen tiated properties, Ax 1 has also been reported to be involved in the c ontrol of cell proliferation. We report that Ax 1 synthesis occurs upo n phorbol 12-myristate 13-acetate (PMA) treatment of A 549 cells and i ts 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 reg ion of the Ax 1 promoter confers the response of the reporter gene to PMA and dexamethasone. This response to PMA and/or dexamethasone invol ves the induction of the synthesis and/or the activity of trans/cis-ac tivating transcriptional factors, Furthermore, we have delineated the mechanism of the transcriptional activation of Ax 1 by PMA and the inv olvement of a specific transcription factor, nuclear factor interleuki n 6 (C/EBP beta).