Signaling and Progression in Prostate Cancer

描述（由申请人提供）：转移性，不依赖激素的前列腺癌（CaP）是无法治愈的。这个多学科项目的目标是阐明CaP从局部和雄激素敏感肿瘤到弥散性和雄激素不依赖型肿瘤进展的信号转导机制。该项目汇集了富有成效和经验丰富的研究人员，他们具有与项目既定目标相关的互补专业知识，并具有信号转导（J. T. Parsons， S. J. Parsons, Weber）、核受体生物学（Paschal）、骨生物学（Guise）、人类前列腺癌病理学（Frierson）、生物统计学（Conaway）和基础和临床前列腺癌转移研究（Theodorescu）的背景。Project 1中，Theodorescu和J. T. Parsons提出评估VEGF、FAK和Rap在CaP进展和骨转移中的作用；Project 2， S. J. Parsons研究了晚期前列腺癌中神经内分泌细胞的生长调控及其对肿瘤整体雄激素依赖性的影响；项目3，M. Weber研究ras介导的信号级联，因为它们影响配体超敏雄激素受体活性；Project 4， Paschal提出研究雄激素受体激活与其核定位控制之间的关系。这一互动项目在很大程度上依赖于所有研究人员的协同技术和科学专业知识。单个项目的生产力由由Theodorescu（行政核心A）领导的高度互动的核心催化，该核心整合了生物统计学家M. Conaway的参与；Guise (Cell, Animal and Imaging Core B)，在骨组织学和组织形态学方面有丰富的经验，熟悉前列腺癌的生物学和用于前列腺癌研究的异种移植模型及其体内成像；Frierson,（组织分析核心C），一位专门研究CaP的外科病理学专家。总之，这些项目和核心整合了不同的技能和专业知识，专注于我们理解CaP肿瘤进展的基础领域，目标是加速开发治疗这种毁灭性疾病的进展。

DESCRIPTION (provided by applicant): Metastatic, hormone independent prostate cancer (CaP) is incurable. The goal of this multidisciplinary Program Project is to elucidate the signal transduction mechanisms that underlie the stepwise events associated with progression of CaP from a localized and androgen sensitive tumor to a disseminated and androgen independent one. The Program brings together productive and experienced investigators with complementary expertise relevant to the stated goal of the Program and backgrounds in signal transduction (J. T. Parsons, S. J. Parsons, Weber), nuclear receptor biology (Paschal), bone biology (Guise), human prostate cancer pathology (Frierson), biostatistics (Conaway) and basic and clinical prostate cancer metastasis research (Theodorescu). In Project 1, Theodorescu and J. T. Parsons propose to evaluate the roles of VEGF, FAK and Rap in CaP progression and metastasis to bone; Project 2, S. J. Parsons studies the regulation of neuroendocrine cell growth within advanced prostate cancers and the impact of such cells on overall tumor dependence on androgen; Project 3, M. Weber studies Ras-mediated signaling cascades as they affect ligand hypersensitive androgen receptor activity; Project 4, Paschal proposes to study the relationship between androgen receptor activation and the control of its nuclear localization. This interactive Program relies heavily on synergistic technical and scientific expertise from all investigators. The productivity of individual Projects is catalyzed by highly interactive Cores led by Theodorescu (Administrative Core A) which integrates the participation of M. Conaway an expert biostatistician; Guise (Cell, Animal and Imaging Core B) who has extensive experience in bone histology and histomorphometry and who is familiar with the biology of prostate cancer and the xenograft models used in prostate cancer research as well as their in vivo imaging; Frierson, (Tissue Analysis Core C), an expert surgical pathologist who specializes in CaP. Together, these Projects and Cores integrate diverse skills and expertise to focus on areas fundamental to our understanding tumor progression in CaP, with the objective of accelerating progress in developing a cure for this devastating disease.