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

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.