CELLULAR AND MOLECULAR BASIS OF PROSTATE METASTASIS TO BONE

这项研究的长期目标是了解 前列腺癌骨转移机制(S)。什么是 前列腺癌趋骨性的细胞和分子基础 在人类身上？骨形态发生蛋白(BMPs)是 在前列腺癌转移中发挥作用的候选人及其倾向 侵袭骨骼。前列腺癌向骨转移的特点是 通过骨硬化性病变和成骨细胞功能的刺激。 目前的工作已经证明了BMP4和BMP4的mRNA和蛋白质都是 7在大鼠和人前列腺中。骨形态发生蛋白-4I型受体的研究进展 在成骨细胞中被鉴定。我们将检验这一假设 BMP-4通过BMP-4以自分泌方式作用于前列腺 感受器。然后我们将调查转移的假说 前列腺癌过度表达BMP-4受体。一种新型骨形态发生蛋白 I受体已通过基于聚合酶链式反应的克隆策略得到鉴定。我们 将通过功能决定这个假定的受体的作用 化验。我们中的一人已经鉴定了内皮素-1基因和蛋白 在人类前列腺癌的骨转移中。另一个 研究人员发现了一种新的骨骼和前列腺癌来源 生长因子-1(BPGF-1)，并赋予转移表型 人LNCaP细胞。这项建议的具体目标是： 1.大鼠骨形态发生蛋白-4和骨形态发生蛋白-7的鉴定和鉴定 和人类前列腺癌。检验BMP的假设 受体在转移性前列腺癌中过度表达。 2.确定内皮素-1在分子生理学中的作用 成骨细胞对前列腺癌的反应和翻译研究结果 将临床数据作为治疗反应的标志。 3.探讨BPGF-1在骨转移及翻译中的作用 作为治疗生物标志物的临床数据集的研究结果 应对和干预。

The long-term goal of this research is to understand the mechanism(s) of metastasis of prostate cancer to bone. What is the cellular and molecular basis of the osteotropism of prostate cancer in humans? The bone morphogenetic proteins (BMPs) are prime candidates to play a role in prostate metastases and propensity to invade bone. The metastases of prostate to bone is characterized by osteosclerotic lesions and stimulation of osteoblast function. Current work has demonstrated both mRNA and protein for BMPs 4 and 7 in rat and human prostate. Very recently BMP-4 type I receptors were identified in osteoblasts. We will examine the hypothesis that BMP-4 acts on prostate in an autocrine manner via BMP-4 receptors. We will then investigate the hypothesis that metastatic prostate carcinoma over expresses BMP-4 receptor. A novel BMP type I receptor has been identified by PCR-based cloning strategy. We will determine the role of this putative receptor by functional assays. One of us has identified endothelin-1 gene and the protein in osseous metastases in human prostate cancer. Another investigator has identified a novel Bone and Prostate derived Growth Factor-1 (BPGF-1) and confers the metastatic phenotype to human LNCap cells. The specific aims of this proposal are: 1. Identification and characterization of BMP-4 and BMP-7 in rat and human prostate cancer. Examine the hypothesis that the BMP receptors are over-expressed in metastatic prostate carcinoma. 2. Determine the function of endothelin-1 in molecular physiology of osteoblastic response to prostate cancer and translate findings to clinical data as a marker of therapeutic response. 3. Investigate the role of BPGF-1 in bone metastases and translate findings to clinical data set as a biomarker of therapeutic response and intervention.