Developmental Biology of the Normal Mouse Prostate

正常小鼠前列腺的发育生物学

• 批准号: 6612919
• 负责人: Susan Kasper
• 金额: $ 28.05万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-15 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6612919
• 关键词: androgens; biomarker; carcinogenesis; cell growth regulation; cell proliferation; gene expression; genetically modified animals; histogenesis; hormone regulation /control mechanism; laboratory mouse; male; molecular cloning; neoplasm /cancer genetics; prostate; prostate neoplasms; protein purification; protein structure function

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.

描述（由申请人提供）：发育中的前列腺具有最高的 随后在成熟成体中停止的细胞增殖速率， 导致生长的静止腺体。我们关注的是 小鼠背侧前列腺叶，并通过质量鉴定蛋白质 发育4周的前列腺中的光谱测定，而成熟的10周中则不存在 周前列腺。这些蛋白质将被进一步表征， 符合以下标准：1）在正常前列腺组织中表达 在4周龄前列腺中发育，2）在10周龄生长中不存在 静止的前列腺，3）由雄激素调节，4）继续表达于 前列腺癌和5）上皮细胞特异性LPB-标记模型将被 用于开发前列腺癌的新模型。我们有合成图 probasin启动子（ARR 2 PB），其是前列腺上皮细胞特异性的， 将高水平的转基因表达靶向小鼠前列腺。的 转基因小鼠模型将使我们能够分析过度表达 这些内源性蛋白质对正常人的生长和分化的影响 前列腺，并确定其在前列腺发育中的作用 癌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： 具体目标一。为了表征先前在本发明中鉴定的蛋白质， 生长4周的前列腺，在10周的生长静止期中不存在 前列腺 具体目标二。为了确定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）。 具体目标三。为了确定这些蛋白质在前列腺中的功能， 使用转基因小鼠模型的肿瘤发生。