MOLECULAR EPIDEMIOLOGY OF PTHRP IN PROSTATE CANCER

描述：（申请人的描述）我们建议研究 前列腺癌中PTHrP的分子流行病学。 这将是 通过研究生产规律和 PTHrP在人前列腺癌中的促生长作用。 我们和 其他人已经证明癌细胞产生PTHrP可以 提供了新的血清和组织标记物，用于检测 疾病与他的申请更相关的是，这种癌细胞产品和 其衍生物有助于恶性肿瘤的微环境 并且可以调节生长和功能。我们将研究细胞， 前列腺癌细胞中PTHrP的分子生物学和临床生物学。我们 我们将在几种类型的细胞中进行研究;细胞 我们在实验室建立的原代细胞系 培养和更新的细胞培养方法。 到怎么 将使用细胞系进行更多的初步研究， 这些主要的文化对于更相关的问题， 通过初步研究。我们将确定 PTHrP及其衍生肽对细胞生长的影响，并阐明PTHrP及其衍生肽对细胞生长的影响。 基因转录，翻译， 加工和分泌PTHrP。我们将阐明分子 这些PTHrPs的产生受细胞因子调节的机制。 PTHrPs本身，以及经典和新认识的增长 因素有待研究的调控分子机制包括 基因表达、翻译和分泌。我们的具体目标是： 确定由前列腺产生的PTHrP的分子形式 细胞，并确定其临床相关性，确定影响， PTHrP及其肽段对人肝癌细胞生长和恶性转化的影响 前列腺细胞，确定PTHrP分泌的分子机制 和信使核糖核酸（mRNA）调节前列腺， 鉴定PTHrP基因表达的转录机制， 前列腺使用的方法包括免疫测定法、免疫组织学、 聚合酶链反应（PCR）和启动子转染分析。 报告质粒。我们的研究将有助于确定 PTHrP的恶性前列腺细胞的生长和功能， 阐明调节的分子机制， PTHrP的产生。这些研究提供了基本的 关于分子和细胞生物学以及临床 关于该多肽在人类中的功能的相关信息 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.