9-顺维甲酸对前列腺癌细胞系LNCaP中同源盒基因NKX3.1表达的影响(英文)

目的:研究9-顺维甲酸对前列腺癌细胞系 LNCaP 中同源盒基因 NKX3.1表达的调节作用。方法:采用流式细胞术、反转录 PCR 和 Western Blot 技术检测9-顺维甲酸对 LNCaP 细胞周期及 NKX3.1表达的影响;构建和转染 NKX3.1启动子-报告基因质粒及其缺失突变体,通过报告基因活性测定,鉴定 NKX3.1启动子中受9顺-维甲酸调控的区域。结果:通过转染及报告基因检测,发现9-顺维甲酸在 LNCaP 细胞中可明显提高 NKX3.1启动子的活性:RT-PCR 和 Western Blot 结果显示,9-顺维甲酸可提高 NKX3.1mRNA 和蛋白的表达,并呈剂量依赖性;通过启动子缺失突变分析,发现 NKX3.1基因上游-936至-921区明显受9-顺维甲酸诱导调节;流式细胞术分析细胞周期的结果显示,9-顺维甲酸可阻止 LNCaP 细胞于 G_1期,减少 G_2/M 期细胞。结论:9-顺维甲酸作为诱导分化剂可阻止 LNCaP 细胞于 G_1期,减少细胞有丝分裂,并明显上调前列腺特异的抑癌基因 NKX3.1的表达。     

ETS rearrangements in prostate cancer

Prostate cancer is a clinically and molecularly heterogeneous disease. Understanding the biologic underpinning of prostate cancer is necessary to best determine how biology is associated with the risk of disease progression and how this understanding might provide insight into the development of novel therapeutic approaches. The focus of this review is on the recently identified common ETS and non-ETS gene rearrangements in prostate cancer. Although multiple molecular alterations have been detected in prostate cancer, a basic understanding of gene fusion prostate cancer should help explain the clinical and biologic diversity, providing a rationale for a molecular subclassification of the disease.     

Expression of NKX3.1 in normal and malignant tissues

BACKGROUND: NKX3.1, a member of the NK-class of homeodomain proteins, is expressed primarily in the adult prostate and has growth suppression and differentiating effects in prostate epithelial cells. METHODS: We performed immunohistochemical analysis for NKX3.1 and PSA expression in 4,061 samples included in a tissue microarray of a broad spectrum of human cancers and normal tissues. RESULTS: NKX3.1 expression was seen in prostate epithelial cells, prostate cancer, normal testis, 9% of primary and 5% of metastatic infiltrating ductal breast carcinoma, and 27% of primary and 26% of metastatic infiltrating lobular breast carcinoma. In a cohort of 474 primary breast cancers with median follow-up over 62.5 month survival, we found no effect of NKX3.1 expression on prognosis. NKX3.1 expression was more restricted than the spectrum of prostate specific antigen expression. CONCLUSIONS: Expression of NKX3.1 is highly restricted and is found primarily in benign and malignant prostatic epithelial cells and also in normal testis and lobular carcinoma of the breast.     

前列腺癌组织RASSF2基因甲基化及蛋白表达的检测及意义

目的:通过检测Ras相关序列家族2(RASSF2)基因在前列腺癌及前列腺增生组织中的甲基化及其蛋白表达情况,探讨该基因的表观失活在前列腺癌发生发展中的作用及意义。方法:获取前列腺癌石蜡包埋组织标本30例(实验组),前列腺增生石蜡包埋组织标本30例(对照组),石蜡组织标本切片后获取相应组织基因组DNA,通过甲基化特异性PCR技术(MSP)检测两组组织中RASSF2基因甲基化情况,通过免疫组织化学技术检测两组组织中RASSF2蛋白表达情况。结果:实验组中,RASSF2基因甲基化发生率为66.7%(20/30),RASSF2蛋白表达缺失发生率为70.0%(21/30);对照组中RASSF2基因甲基化发生率为6.7%(2/30),RASSF2蛋白表达缺失发生率为3.3%(1/30)。实验组RASSF2基因甲基化发生率显著高于对照组,差异有统计学意义(P<0.05);实验组RASSF2蛋白表达缺失发生率显著高于对照组,差异亦有统计学意义(P<0.05)。RASSF2基因异常甲基化与其蛋白表达缺失具有显著相关性(P<0.05)。结论:RASSF2基因的表观失活与前列腺癌的发生具有相关性,RASSF2基因的表观失活有望成为前列腺癌的分子诊断及治疗靶点。     

同源框基因NKX3.1在前列腺癌组织中的表达及意义

目的　探讨同源框基因NKX3.1在前列腺癌中的表达意义。　方法　采用半定量RT PCR检测前列腺癌、良性前列腺、非前列腺组织标本NKX3.1mRNA表达状况并对其扩增产物进行测序。　结果　 76例前列腺组织中 ,NKX3.1表达 75例 ,表达率 98.7%。 96例非前列腺组织标本中 ,除 2例睾丸组织、1例乳腺组织有NKX3.1表达外 ,肾、膀胱、肝、回肠、脂肪、皮肤组织无 1例表达。前列腺癌组织NKX3.1表达量明显增高 ,良性前列腺增生组织表达量明显减弱 (P <0 .0 1) ;晚期前列腺癌组织NKX3.1表达明显高于早期前列腺癌 (P <0 .0 5 ) ;低分化前列腺癌表达高于中高分化前列腺癌 (P <0 .0 5 ) ;激素依赖性前列腺癌表达高于激素非依赖性前列腺癌 (P <0 .0 1)。NKX3.1表达高低与前列腺体积和血清总PSA浓度无关 (P >0 .0 5 )。　结论　NKX3.1基因具有前列腺组织特异性 ,其表达状况与前列腺癌分期、分级相关。NKX3.1表达对于判断前列腺癌病理生物学特性和前列腺癌治疗有重要意义。     

Interspecies comparison of prostate cancer gene‐expression profiles reveals genes associated with aggressive tumors

Prostate cancer (PC) is a heterogeneous disease whose aggressive phenotype is the second leading cause of cancer‐related death in men. The identification of key molecules and pathways that play a pivotal role in PC progression towards an aggressive form is crucial. A major effort towards this end has been taken by global analyses of gene expression profiles. However, the large body of data did not provide a definitive idea about the genes which are associated with the aggressive growth of PC. In order to identify such genes, we performed an interspecies comparison between several human data sets and high quality microarray data that we generated from the transgenic adenocarcinoma of mouse prostate (TRAMP) strain. The TRAMP PC mimics the histological and pathological appearance as well as the aggressive phenotype of human PC (huPC). Analysis of the microarray data, derived from microdissected TRAMP specimens removed at different stages of the disease yielded genetic signatures delineating the TRAMP PC development and progression. Comparison of the TRAMP data with a set of genes representing the core expression signature of huPC yielded a limited set genes. Some of these genes are known predictors of poor prognosis in huPC. Interestingly, the modulation of genes responsible for the invasive phenotype of huPC occurs in TRAMP already during the transition to prostate intraepithelial neoplasia (PIN) and onwards to localized tumors. We therefore suggest that critical oncogenic events leading to an aggressive phenotype of huPC can be studied in the PIN stage of TRAMP. Prostate 69:1034–1044, 2009. © 2009 Wiley‐Liss, Inc.