Genes Modulated by Soy in Prostate Cancer Progression

描述(由申请人提供)： 进展为雄激素非依赖性前列腺癌仍是前列腺癌(CAP)相关死亡的主要原因。设计能够有效延缓或阻止雄激素非依赖性前列腺癌由雄激素依赖型前列腺癌向雄激素非依赖型前列腺癌发展的预防和治疗药物一直是CAP研究的重点之一。以前的研究表明，大豆含有抑制CAP进展的生物活性成分。这项试验性应用的重点是评估大豆异黄酮染料木素和大豆植物化学浓缩物(SPC)对前列腺癌进展到雄激素非依赖性的预防效果，并确定Genistein和SPC作用的分子靶点。假设是，生物活性大豆成分可以防止或延缓雄激素非依赖性和激素抵抗型CAP的进展。 具体目的1是确定金雀异黄素和SPC在防止CAP从雄激素依赖表型向雄激素非依赖性表型进展方面的剂量依赖效应。将使用从雄激素敏感帽到雄激素非依赖性帽的原位进展的动物模型。最终的原发肿瘤重量将被用作主要结果，以确定染料木素或SPC在预防进展为雄激素非依赖性前列腺癌方面的剂量依赖效应。淋巴结转移和肺转移将被用来确定染料木素或SPC在雄激素非依赖性进展过程中预防转移的剂量依赖效应。具体目的2是应用基因芯片技术筛选可能与金雀异黄素和SPC预防雄激素非依赖性前列腺癌有关的前列腺癌基因。从特定目标1的动物研究中提取的肿瘤样本将被用于制备用于基因芯片分析的总RNA。通过进行数据挖掘和分析，我们希望确定可能导致雄激素非依赖性前列腺癌进展的几个基因，这些基因对金雀异黄素和/或SPC作用敏感。这些经过验证的基因可能是替代终点标记的候选，用于评估大豆预防试验对CAP进展的有效性。这一试验性应用的结果将有助于深入了解大豆生物活性成分在防止CAP进展为雄激素非依赖性表型和了解分子作用机制方面的潜在应用。

DESCRIPTION (provided by applicant): Progression to androgen-independent prostate tumor is still the major cause of prostate cancer (CAP) related death. Design of preventive and therapeutic agents that can effectively delay or prevent progression of androgen-independent prostate tumor from androgen-dependent prostate tumor has been one of the priorities in CaP research. Previous studies have suggested that soybean contains bioactive components that inhibit the progression of CaP. This pilot application is focused on evaluating the preventive effects of soy isoflavone genistein and soy phytochemical concentrate (SPC) on prostate tumor progression to androgen-independence and on identifying the molecular targets of genistein and SPC actions. The hypothesis is that bioactive soy components may prevent or delay the progression of androgen-independent and hormone-refractory CaP. Specific Aim 1 is to determine the dose-dependent effects of genistein and SPC on prevention of CaP progression to androgen-independent phenotype from androgen-dependent phenotype. An animal model for orthotopic progression of androgen-sensitive CaP to androgen-independent CaP will be used. Final primary tumor weight will be used as the primary outcome to determine the dose-dependent effects of genistein or SPC on prevention of progression to androgen-independent prostate tumors. Both lymph nodes metastases and lung metastases will be used to determine the dose-dependent effects of genistein or SPC on prevention of metastasis during progression to androgen-independence. Specific Aim 2 is to apply cDNA microarray assays to identify prostate tumor genes that may be responsible for the effects of genistein and SPC on prevention of androgen-independent prostate tumor. Tumor samples derived from the animal study in Specific Aim 1 will be used to prepare total RNA for cDNA microarray assays. By performing data mining and analysis, we expect to identify several genes that may be responsible for the progression of androgen-independent prostate tumors and are sensitive to the genistein and/or SPC actions. These verified genes may be candidates of surrogate endpoint markers for evaluating the efficacy of soy prevention trials on CaP progression. Results derived from this pilot application will shed insight into the potential application of soy bioactive components to the prevention of CaP progression to androgen-independent phenotype and the understanding of molecular mechanisms of action.