TRANSCRIPTIONAL REGULATION OF THE HUMAN CD9 GENE - CHARACTERIZATION OF THE 5'-FLANKING REGION

The CD9 antigen, initially discovered on B lineage leukemic cells, bel ongs to the tetraspan superfamily of surface molecules. If no precise function has been assigned to any of these molecules, there are some i ndications that they could be involved in cell adhesion and cell migra tion, as well as malignant progression. The CD9 antigen is associated with surface proteins such as VLA integrins or HB-EGF precursor. Trans fection of CD9 in melanoma cells reduces tumor growth and metastasis. The heterogenous distribution of the CD9 antigen suggests a complex re gulation of its expression. We have previously characterized the CD9 g ene and shown that transcription could be initiated at several sites i n the TATA-less 5 '-flanking region. We show here, using as a model tw o human leukemic cell lines with erythromegakaryocytic potential, HEL and K562, that the [-205,-154] region supports a promoter activity whe n cloned ahead of a CAT reporter gene. Mutagenesis analysis suggested the presence of a positive element located within the [-170,-154] regi on. Gel shift experiments using HEL extracts were compatible with the binding of the transcriptional factor Spl to the [-237,-205] region an d indicated that a non-identified protein binds to the 3 ' end of the [-205,-154] region.