TRANSCRIPTIONAL ACTIVATION OF THE H-FERRITIN GENE IN DIFFERENTIATED CACO-2 CELLS PARALLELS A CHANGE IN THE ACTIVITY OF THE NUCLEAR FACTOR BBF

In this paper, we examine the mechanisms that regulate the expression of the heavy (H) ferritin subunit in the colon carcinoma Caco-2 cell l ine allowed to differentiate spontaneously in vitro. The differentiati on process of these cells in continuous culture is accompanied by an a ccumulation of the mRNA coding for the apoferritin H chain. The analys is of Caco-2 subclones stably transfected with an H-chain promoter-chl oramphenicol acetyltransferase (CAT) construct revealed that the mRNA increase is paralleled by an enhanced transcription of the H gene, dri ven by the - 100 to + 4 region of the H promoter. The H gene transcrip tional activation seems to be a specific feature of differentiated Cac o-2 cells, since the activity of other promoters did not change upon d ifferentiation. The - 100 to + 4 region of the H promoter binds a tran scription factor called Bbf (B-box binding factor); electrophoretic-mo bility-shift-assay analyses showed that the retarded complex due to Bb f-H promoter interaction is significantly increased in the differentia ted cells. We propose that the activation of H-ferritin gene expressio n may be associated with the establishment of a differentiated phenoty pe in Caco-2 cells, and that the H-ferritin gene transcriptional upreg ulation is accompanied by a modification in the activity of the transc ription factor Bbf.