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题目:: Identification of genes regulated in adrenal glands of Ftz-F1 transgenic mice
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状态:: 发布时间June 12, 2010 , 更新时间 May 2, 2014 , 提交时间 Sept. 25, 2006,
物种:: Mus musculus
摘要:: SF-1, a transcription factor belonging to the nuclear receptor superfamily, has a pivotal role for adrenogonadal development in humans and mice. A constant feature of childhood adrenocortical tumors (ACT) is SF-1 amplification and overexpression. Using an inducible cellular system, here we show that SF-1 overexpression increases human adrenocortical cell proliferation through opposing effects on cell cycle and apoptosis. SF-1 overexpression also selectively modulates steroidogenesis, reducing cortisol and aldosterone secretion. We identified a novel pro-apoptotic factor for adrenocortical cells, NOV/CCN3, whose levels are significantly reduced by SF-1 overexpression in human adrenocortical cells and are also reduced in primary adrenal tumors. Moreover, Sf-1 overexpression triggers adrenocortical hyperplasia and tumor formation in mice. These tumors express gonadal markers and activated Stat3. Our studies reveal the critical role of SF-1 gene dosage for adrenocortical tumorigenesis and constitute a rationale for the development of drugs targeting SF-1 transcriptional activity for ACT therapy. Keywords: comparative gene expression Gene expression profiles were analyzed by two-color microarrays in transgenic mice from line #56 heterozygous or homozygous for the transgene, male or female and of different ages. Profiles from each transgenic mouse were directly compared to a sex- and age-matched wild-type littermate. For each experimental point, two technical replicates (dye-swaps) were examined. Array # Age Sex Transgene copy # Cy3 Cy5 16682 10 days M 1 WT transgenic 16479 10 days M 1 transgenic WT 16683 10 days M 1 WT transgenic 16625 10 days M 1 transgenic WT 16685 10 days F 1 WT transgenic 16680 10 days F 1 transgenic WT 16516 4 months M 2 WT transgenic 16452 4 months M 2 transgenic WT 16517 4 months M 2 WT transgenic 16453 4 months M 2 transgenic WT 16518 4 months F 2 WT transgenic 16475 4 months F 2 transgenic WT
实验种类:: transcription profiling by array
样本量:: 24
实验设计:
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数据号:: E-GEOD-5912, GSE5912
数据状态:: 无法自动分析，您可以尝试手动分析数据。

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