Developmental Biology of the Normal Mouse Prostate

描述（由申请人提供）： 发育中的前列腺具有最高的 细胞增殖率随后在成熟成人中停止， 导致腺体生长静止。我们专注于形态发生 小鼠背前列腺叶并通过质量鉴定了蛋白质 发育中 4 周前列腺的光谱测定，在成熟 10 周前列腺中不存在 周前列腺。这些蛋白质将被进一步表征，并且那些 满足以下标准： 1) 在正常前列腺中表达 4 周龄前列腺发育，2) 10 周龄前列腺发育不存在 静止的前列腺，3）受雄激素调节，4）继续在 前列腺癌的 LPB-Tag 模型和 5) 上皮细胞特异性将是 用于开发前列腺癌的新模型。我们有复合的 probasin 启动子 (ARR2PB) 是前列腺上皮细胞特异性的，并且 针对小鼠前列腺的高水平转基因表达。的 转基因小鼠模型将使我们能够分析过度表达的影响 这些内源性蛋白质对正常细胞的生长和分化有影响 前列腺并确定它们在前列腺发育中的作用 癌症。我们的假设是调节正常前列腺的蛋白质 形态发生可能促进前列腺癌的发展。 该提案的具体目标是： 具体目标 I. 表征先前在 生长 4 周的前列腺在 10 周生长静止期中不存在 前列腺。 具体目标二。为了定义这些蛋白质在发育中的表达 前列腺并确定它们是否在前列腺癌中重新表达（使用 前列腺癌的 LPB-Tag 模型）。 具体目标 III.确定这些蛋白质在前列腺中的功能 使用转基因小鼠模型进行肿瘤发生。

DESCRIPTION (provided by applicant): The developing prostate has the highest rate of cell proliferation which subsequently ceases in the mature adult, resulting in a growth quiescent gland. We have focused on the morphogenesis of the mouse dorsal prostatic lobes and have identified proteins by mass spectrometry in the developing 4 week prostate that are absent in the mature 10 week prostate. These proteins will be characterized further and those which meet the criteria that they are: 1) expressed during normal prostate development in the 4 week old prostate, 2) absent in the 10 week growth quiescent prostate, 3) regulated by androgens, 4) continue to be expressed in the LPB-Tag model for prostate cancer and 5) epithelial cell specific will be utilized to develop novel models for prostate cancer. We have the composite probasin promoter (ARR2PB) which is prostate epithelial cell specific and which targets high levels of transgene expression to the mouse prostate. The transgenic mouse models will allow us to analyze the effects of over-expressing these endogenous proteins on the growth and differentiation of the normal prostate gland and to determine their role in the development of prostate cancer. Our HYPOTHESIS is that proteins that regulate normal prostate morphogenesis may promote the development of prostate cancer. The Specific Aims of this proposal are: Specific Aim I. To characterize the proteins previously identified in the growing 4 week prostate which are absent in the 10 week growth quiescent prostate. Specific Aim II. To define the expression of these proteins in the developing prostate and determine whether they are re-expressed in prostate cancer (using the LPB-Tag model for prostate cancer). Specific Aim III. To determine the function of these proteins in prostate tumorigenesis using the transgenic mouse model.