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

H Schorle
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Abstract

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.

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[关于转录因子家族AP-2在发育和疾病中的作用——来自小鼠模型的教训]。
为了分析转录因子ap -2 γ在小鼠体内功能获得和功能丧失的后果,采用原核注射法建立并分析了携带乳腺特异性转基因的小鼠。构成性和条件性基因敲除小鼠补充了分析结果,显示了特定组织功能丧失的后果。AP-2在乳腺中自身表达的增加导致增殖增强,并通过加速凋亡来补偿。仅在与第二种转基因小鼠MMTV-ErbB2肿瘤小鼠模型交配后,观察到其对肿瘤进展的影响。因此,AP-2可能影响乳腺肿瘤的进展,但不影响肿瘤的发生。敲除小鼠模型显示,ap -2 γ对胚胎外细胞至关重要,表明其在滋养细胞谱系中的作用。这些研究和其他研究表明,ap -2 γ可能是一种使未分化前体或瞬时扩增细胞增殖的分子。肿瘤中的再表达与去分化和进展相关。
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