Gene expression and regulation of transcription factor activator protein-2 alpha in human mast cells

Abstract

The transcription factor activator protein (AP)-2 regulates cell-type specific gene expression during development and differentiation, but its role in mast cell development has so far not been explored. Gene expression and regulation of AP2 was assessed in normal skin, diseases with increased mast cell numbers, and in vitro models of mast cell differentiation. AP-2alpha-protein was not detectable in normal skin but in mastocytoma lesional mast cells. AP-2alpha-mRNA and -protein were also detected in leukemic mast cells (HMC-1), in the adherent fraction of peripheral blood (PBMC) and umbilical cord blood mononuclear cells (CBMC), and AP-2alpha-mRNA at low levels in isolated-purified mast cells. During culture with fibroblast supernatants or SCF, AP-2alpha-mRNA was de novo expressed in KU812-cells, maintained at about the same level in PBMC and CBMC, and upregulated in HMC-1-cells. On extended culture, a down-regulation was noted at mRNA and/or protein levels. In contrast, tryptase expression increased in all cells throughout culture, as did c-Kit in normal cells, whereas in both leukemic cell lines, c-Kit was maintained unchanged at about the same level. These findings suggest a continuous activation of AP-2alpha in mastocytomas and mast cell leukemia and its transient upregulation during c-Kit dependent early steps of normal mast cell differentiation.