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肿瘤仍然是前列腺癌（CAP）相关死亡的主要原因。设计能够有效延缓或阻止雄激素依赖性前列腺肿瘤向雄激素非依赖性前列腺肿瘤进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。该试验应用的重点是评估大豆异黄酮和大豆植物化学浓缩物（SPC）对前列腺肿瘤进展到雄激素非依赖性的预防作用，并确定染料木素和SPC作用的分子靶点。该假说是生物活性大豆成分可能会阻止或延迟雄激素非依赖性和难治性CaP的进展。 具体目的1是确定染料木黄酮和SPC对预防CaP从雄激素依赖性表型进展为雄激素非依赖性表型的剂量依赖性作用。将使用雄激素敏感性CaP原位进展为雄激素非依赖性CaP的动物模型。最终原发肿瘤重量将用作主要结局，以确定染料木黄酮或SPC对预防进展为雄激素非依赖性前列腺肿瘤的剂量依赖性作用。淋巴结转移和肺转移将用于确定染料木黄酮或SPC在进展至雄激素非依赖性期间对转移预防的剂量依赖性作用。具体目标2是应用cDNA微阵列分析，以确定前列腺肿瘤的基因，可能是负责的染料木素和SPC对雄激素非依赖性前列腺肿瘤的预防效果。特定目标1中动物研究的肿瘤样本将用于制备cDNA微阵列试验的总RNA。通过进行数据挖掘和分析，我们希望确定几个基因，可能是负责雄激素非依赖性前列腺肿瘤的进展，并敏感的染料木素和/或SPC的行动。这些经过验证的基因可能是替代终点标志物的候选者，用于评估大豆预防试验对CaP进展的功效。来自这个试点应用的结果将深入了解大豆生物活性成分的潜在应用，以防止CaP进展到雄激素非依赖性表型和分子作用机制的理解。

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.