MOLECULAR EPIDEMIOLOGY OF PTHRP IN PROSTATE CANCER

描述：(申请人的描述)我们建议研究 前列腺癌甲状旁腺素受体的分子流行病学研究。这将是 通过学习生产和生产的规律来实现 PTHrP在人前列腺癌中的促生长作用。我们和 其他研究表明，癌细胞产生的甲状旁腺素rp可以 提供新的血清和组织标记物，以确定其存在和程度 疾病。与他的应用更相关的是，这种癌细胞产品和 其衍生物有助于肿瘤的微环境。 并能调节生长和功能。我们将研究细胞， 前列腺癌PTHrP的分子生物学和临床生物学研究。我们 将在几种类型的细胞制备中进行我们的研究； 我们在实验室中建立的原代细胞系 培养，以及细胞培养的新方法。我们的总体做法 将使用细胞系进行更多的初步研究并使用 更相关的问题的主要文化 以前期研究为重点。我们将确定以下影响： PTHrP及其衍生多肽对细胞生长的影响 基因转录、翻译、 甲状旁腺素rP的加工和分泌。我们将阐明分子 这些PTHrp的产生受 PTHrp本身，以及由经典和新欣赏的增长 各种因素。有待研究的分子调控机制包括 基因的表达、翻译和分泌。我们的具体目标是： 确定由前列腺产生的甲状旁腺素rP的分子形式 细胞，并确定它们的临床相关性，确定 PTHrP及其多肽对人肝癌细胞生长和恶变的影响 前列腺细胞，确定PTHrP分泌的分子机制 和前列腺中的信使核糖核酸(MRNA)调节，以及 确定甲状旁腺激素受体基因表达的转录机制 前列腺。将使用的方法包括免疫分析，免疫组织学， 聚合酶链式反应(聚合酶链式反应)和启动子-2的转染分析 报道质粒。我们的研究将有助于确定 甲状旁腺素受体对恶性前列腺细胞生长和功能的影响 阐明调控的分子机制 PTHrP在这种恶性肿瘤中的产生。这些研究应该提供基本的 关于分子和细胞生物学以及临床的信息 关于该多肽在人体内功能的相关信息 前列腺癌。

DESCRIPTION: (Applicant's Description) We propose to study the molecular epidemiology of PTHrP in prostate cancer. This will be accomplished by studying the regulation of the production and the growth-promoting effects of PTHrP in human prostate cancers. We and others have demonstrated that PTHrP production by cancer cells can provide novel serum and tissue markers for the presence and extent of disease. More relevant to his application, this cancer cell product and its derivatives contribute to the microenvironment of the malignancy and can regulate growth and function. We shall study the cellular, molecular, and clinical biology of PTHrP in prostate cancer cells. We shall conduct our studies in several types of cell preparartions; cell lines that we have established in our laboratory, primary cell cultures, and newer methods of cell culture. Our general approach will be to use cell lines for more preliminary studies and to use the primary cultures for the more relevant questions that become focused by the preliminary studies. We shall identify the effects of PTHrP and its derived peptides on cell growth and elucidate the mechanisms of the regulation of the gene transcription, translation, processing, and secretion of PTHrP. We shall elucidate the molecular mechanisms by which the production of these PTHrPs is regulated by the PTHrPs, themselves, and by classical and newly-appreciated growth factors. The molecular mechanisms of regulation to be studies include gene expression, translation, and secretion. Our specific Aims are to: determine the molecular forms of PTHrP that are produced by prostate cells and identify their clinical correlates, determine the effects of PTHrP and its peptides on the growth and malignant transformation of prostate cells, identify the molecular mechanisms of PTHrP secretion and messenger ribonucleic acid (mRNA) regulation in the prostate, and identify the transcriptional mechanisms of PTHrP gene expression in the prostate. The methods to be used include immunoassay, immunohistology, polymerase chain reaction (PCR), and transfection analysis of promoter- reporter plasmids. Our studies will help to identify the importance of PTHrP for the growth and function of malignant prostate cells and elucidate the molecular mechanisms that underlie the regulation of PTHrP production in this malignancy. These studies should provide basic information about the molecular and cellular biology and clinically relevant information about the function of this polypeptide in human prostate cancer.