[On the role of transcription factor family AP-2 for development and disease--lessons from mouse models]

To analyze the consequence of ,gain of function' and ,loss of function' of transcription factor AP-2gamma in mice Using pronuclear injection, mice harbouring a mammary gland specific transgene were established and analyzed. Constitutive and conditional knockout mice complement the analysis, showing the consequences of loss of function for specific tissues. Gain of AP-2 expression on it's own in mammary gland results in enhanced proliferation which is compensated by accelerated apoptosis. Only after mating with a second transgenic mouseline, the MMTV-ErbB2 oncomouse model, an effect on tumor progression was observed. Hence, AP-2 might influence progression, but not initiation of mammary tumors. Knockout mouse models reveal that AP-2gamma is essential for the extraembryonic cells indicating a role for trophoblast cell lineage These and other studies indicate that AP-2gamma might be a molecule which enables proliferation of undifferentiated precursors or transient amplifying cells. Reexpression in tumors correlates with dedifferentiation and progression.