Developmental Biology of the Normal Mouse Prostate

描述(申请人提供)：发育中的前列腺最高 在成熟的成体中随后停止的细胞增殖速度， 从而形成生长静止的腺体。我们主要关注的是 小鼠的背侧前列腺叶，并通过质量鉴定了蛋白质 发育中的4周成熟10例缺失的前列腺的光谱分析 一周的前列腺癌。这些蛋白质将被进一步鉴定，而那些 符合以下标准：1)在正常前列腺组织中表达 4周龄前列腺发育，2)10周生长缺失 静止的前列腺，3)受雄激素调节，4)继续在 前列腺癌和上皮细胞特异性的LPB-TAG模型将是 用于开发前列腺癌的新模型。我们有合成材料 前盆启动子(ARR2PB)，它是前列腺上皮细胞特异性的， 靶向小鼠前列腺的高水平转基因表达。这个 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人生长和分化的影响 前列腺癌及其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生发展。 这项建议的具体目标是： 具体目标一.鉴定先前在 生长4周的前列腺在10周的生长停滞中缺失 前列腺。 特定目的II.明确这些蛋白在发育过程中的表达 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标签模型)。 特定目的III.确定这些蛋白质在前列腺中的功能 利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.