全基因體分析雄激素受體和雌激素受體結合位點上的單一核酸多型性與

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Title:	全基因體分析雄激素受體和雌激素受體結合位點上的單一核酸多型性與
Authors:	鮑柏穎(Bo-Ying Bao);(Huang SP)
Contributors:	藥學院藥學系
Date:	2013-07-31
Issue Date:	2012-06-15 11:44:34 (UTC+8)
Abstract:	雄激素受體和雌激素受體為轉?因子，且在前?腺的發展和癌變中扮演著非常關鍵的角色，因此要?解前?腺癌的病?生?學，尋找被雄激素受體與雌激素受體調節的基因是必要的。我們假設在雄激素受體或雌激素受體與去氧核?核酸結合位點上的單一核酸多型性，可能會影響雄激素受體或雌激素受體靶基因的表達，並有可能造成前?腺癌的?感性，或影響前?腺癌根除術(未轉移前?腺癌的標準初步治?法)和雄激素去除?法(未轉移晚期或已轉移前?腺癌的標準初步治?法)的預後。此研究的具體目標是：1) 全基因體分析雄激素受體和雌激素受體與去氧核?核酸結合位點。2) 全基因體尋找位於雄激素受體和雌激素受體結合位點上的單一核酸多型性。3) 以病?對照及?發追蹤研究，全面的評估雄激素受體和雌激素受體結合位點上的單一核酸多型性，是否與前?腺癌的風險或前?腺癌根除術和雄激素去除?法的預後有關。4) 研究雄激素受體和雌激素受體結合位點上的單一核酸多型性附近的雄激素受體和雌激素受體靶基因，在前?腺癌的?感性中潛在的功能。5) 最後，?用組織晶片測試候選基因的表達是否與前?腺癌的發展有關。這項研究是獨特和新穎的，因為我們透過全基因體的分析雄激素受體和雌激素受體結合位點上的單一核酸多型性，?發現新的前?腺癌?感基因型及預後標誌，這項研究的成果?但值得特別注意，並可幫助我們?解造成前?腺癌的病因，進而研發出?有效的治?方法。 The androgen receptor (AR) and estrogen receptor (ER) play key roles as transcriptional factor in prostate development and carcinogenesis. Identification of androgen- and estrogen-regulated genes is essential to elucidate the pathophysiology of AR and ER in prostate cancer (PCa). Therefore, we propose that single-nucleotide polymorphisms (SNPs) located at AR and ER binding sites are likely to affect the expression of the AR and ER target genes, and may contribute to the susceptibility of human PCa, the prognosis after radical prostatectomy (RP) (the standard initial therapy for localized PCa), and the prognosis after androgen deprivation therapy (ADT) (the standard initial therapy for locally advanced or metastatic PCa). The objectives of this proposed project are: 1) To perform a genome-wide analysis of AR and ER binding sites. 2) To identify SNPs located on the AR and ER binding sites in the genome-wide scale. 3) To comprehensively evaluate the association of each SNP on AR and ER binding sites with the risk of PCa and prognosis after RP and ADT in the population studies. 4) To investigate the potential functional significance of the SNPs, nearby AR/ER target genes, and their association with PCa susceptibility. 5) Finally, to correlate candidate gene expression with PCa progression using tissue microarray. This proposed study is unique and novel because we aim to discover potential prognostic markers and susceptibility gene variants for PCa via a whole genome AR/ER binding site association design. In addition, findings from this study will be particularly noteworthy and help us understand the etiology of the PCa.
Appears in Collections:	[Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources] Research reports

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